IkappaBalpha

Summary

Gene Symbol: IkappaBalpha
Description: NFKB inhibitor alpha
Alias: IKBA, MAD-3, NFKBI, NF-kappa-B inhibitor alpha, I-kappa-B-alpha, IkappaBalpha, ikB-alpha, major histocompatibility complex enhancer-binding protein MAD3, nuclear factor of kappa light chain gene enhancer in B-cells, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Species: human

Top Publications

  1. ncbi NFKB and NFKBI polymorphisms in relation to susceptibility of tumour and other diseases
    X F Sun
    Department of Oncology, Institute of Biomedicine and Surgery, University of Linkoping, Linkoping, Sweden
    Histol Histopathol 22:1387-98. 2007
  2. doi Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K, Akt cascade and promotion of NF-kappaB/p300 binding in human synovial fibroblasts
    Kwok Man Tong
    Department of Orthopaedics, Taichung Veterans General Hospital, Taichung, Taiwan
    Cell Signal 20:1478-88. 2008
  3. ncbi The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes
    Lakshmanan Ganesh
    Vaccine Research Center, NIAID, National Institutes of Health, Building 40, Room 4502, MSC 3005, 40 Convent Drive, Bethesda, Maryland 20892 3005, USA
    Nature 426:853-7. 2003
  4. doi Activation of the IκB kinase complex by HTLV-1 Tax requires cytosolic factors involved in Tax-induced polyubiquitination
    Yuri Shibata
    Department of Cancer Biology, Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Shirokane dai, Minato ku, Tokyo 108 8639, Japan
    J Biochem 150:679-86. 2011
  5. pmc Human immunodeficiency virus-1 Tat activates NF-κB via physical interaction with IκB-α and p65
    Giuseppe Fiume
    Department of Experimental and Clinical Medicine, University of Catanzaro Magna Graecia, Viale Europa Germaneto, 88100 Catanzaro, Italy
    Nucleic Acids Res 40:3548-62. 2012
  6. ncbi Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling
    Yaya Wang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People s Republic of China
    Nat Immunol 7:139-47. 2006
  7. ncbi Critical roles of threonine 187 phosphorylation in cellular stress-induced rapid and transient activation of transforming growth factor-beta-activated kinase 1 (TAK1) in a signaling complex containing TAK1-binding protein TAB1 and TAB2
    Pattama Singhirunnusorn
    Division of Pathogenic Biochemistry, Institute of Natural Medicine, 21st Century Center of Excellence COE Program, Toyama Medical and Pharmaceutical University, Toyama 930 0194, Japan
    J Biol Chem 280:7359-68. 2005
  8. ncbi Hiv-1 Tat can substantially enhance the capacity of NIK to induce IkappaB degradation
    X Li
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Biochem Biophys Res Commun 286:587-94. 2001
  9. doi HIV-1 Tat dysregulation of lipopolysaccharide-induced cytokine responses: microbial interactions in HIV infection
    Howard C H Yim
    Cytokine Biology Group, Department of Paediatrics and Adolescent Medicine, China bBio Screening Unit, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
    AIDS 23:1473-84. 2009
  10. pmc HIV replication in CD4+ T lymphocytes in the presence and absence of follicular dendritic cells: inhibition of replication mediated by α-1-antitrypsin through altered IκBα ubiquitination
    Xueyuan Zhou
    Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA
    J Immunol 186:3148-55. 2011

Research Grants

  1. CONTROL OF TNF SIGNALING BY NFKB
    ALBERT BALDWIN JR; Fiscal Year: 2003
  2. Alcohol, iNOS upregulation, leaky gut & liver disease
    Ali Keshavarzian; Fiscal Year: 2009
  3. MEDIATORS AND MODIFIERS OF NF-kappaB IN INSULIN RESISTANCE
    Steven E Shoelson; Fiscal Year: 2010
  4. NF-kappaB Regulation by Androgen Receptor
    ALBERT BALDWIN JR; Fiscal Year: 2004
  5. NEOADJUVANT THERAPY OF OR CANCER BY INHIBITING NF-KAPPAB
    Cun Yu Wang; Fiscal Year: 2003
  6. Mechanism of Constitutive NF-kappa B Activity
    Shigeki Miyamoto; Fiscal Year: 2007
  7. Negative regulation of NF-kB and inflammation by TAX1BP1
    Edward W Harhaj; Fiscal Year: 2012
  8. Alex B Lentsch; Fiscal Year: 2014
  9. JAROSLAW WALDEMAR ZMIJEWSKI; Fiscal Year: 2015
  10. FUNCTIONAL ANALYSIS OF THE MOUSE-PELLE-LIKE KINASE
    Maureen Harrington; Fiscal Year: 2003

Detail Information

Publications224 found, 100 shown here

  1. ncbi NFKB and NFKBI polymorphisms in relation to susceptibility of tumour and other diseases
    X F Sun
    Department of Oncology, Institute of Biomedicine and Surgery, University of Linkoping, Linkoping, Sweden
    Histol Histopathol 22:1387-98. 2007
    ..In this review, we focus on polymorphisms of the NFKB and NFKBI genes in relation to development of common inflammatory diseases including ulcerative colitis (UC), Crohn's ..
  2. doi Leptin induces IL-8 expression via leptin receptor, IRS-1, PI3K, Akt cascade and promotion of NF-kappaB/p300 binding in human synovial fibroblasts
    Kwok Man Tong
    Department of Orthopaedics, Taichung Veterans General Hospital, Taichung, Taiwan
    Cell Signal 20:1478-88. 2008
    ..These results suggest that leptin increased IL-8 production in synovial fibroblast via the OBRl/JAK2/STAT3 pathway, as well as the activation of IRS1/PI3K/Akt/NF-kappaB-dependent pathway and the subsequent recruitment of p300...
  3. ncbi The gene product Murr1 restricts HIV-1 replication in resting CD4+ lymphocytes
    Lakshmanan Ganesh
    Vaccine Research Center, NIAID, National Institutes of Health, Building 40, Room 4502, MSC 3005, 40 Convent Drive, Bethesda, Maryland 20892 3005, USA
    Nature 426:853-7. 2003
    ..Through its effects on the proteasome, Murr1 acts as a genetic restriction factor that inhibits HIV-1 replication in lymphocytes, which could contribute to the regulation of asymptomatic HIV infection and the progression of AIDS...
  4. doi Activation of the IκB kinase complex by HTLV-1 Tax requires cytosolic factors involved in Tax-induced polyubiquitination
    Yuri Shibata
    Department of Cancer Biology, Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Shirokane dai, Minato ku, Tokyo 108 8639, Japan
    J Biochem 150:679-86. 2011
    ..These results obtained through our cell-free assay suggest that K63-linked polyubiquitination is critical, but linear polyubiquitination is dispensable or insufficient for Tax-induced IKK activation...
  5. pmc Human immunodeficiency virus-1 Tat activates NF-κB via physical interaction with IκB-α and p65
    Giuseppe Fiume
    Department of Experimental and Clinical Medicine, University of Catanzaro Magna Graecia, Viale Europa Germaneto, 88100 Catanzaro, Italy
    Nucleic Acids Res 40:3548-62. 2012
    ..Our results support a novel mechanism of NF-κB activation via physical interaction of Tat with IκB-α and p65, and may contribute to further insights into the deregulation of the inflammatory response by HIV-1...
  6. ncbi Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling
    Yaya Wang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People s Republic of China
    Nat Immunol 7:139-47. 2006
    ..Thus, beta-arrestins are essential negative regulators of innate immune activation via TLR-IL-1R signaling...
  7. ncbi Critical roles of threonine 187 phosphorylation in cellular stress-induced rapid and transient activation of transforming growth factor-beta-activated kinase 1 (TAK1) in a signaling complex containing TAK1-binding protein TAB1 and TAB2
    Pattama Singhirunnusorn
    Division of Pathogenic Biochemistry, Institute of Natural Medicine, 21st Century Center of Excellence COE Program, Toyama Medical and Pharmaceutical University, Toyama 930 0194, Japan
    J Biol Chem 280:7359-68. 2005
    ..These results indicate critical roles of Thr-187 phosphorylation in the stress-induced rapid and transient activation of TAK1 in a signaling complex containing TAB1 and TAB2...
  8. ncbi Hiv-1 Tat can substantially enhance the capacity of NIK to induce IkappaB degradation
    X Li
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA
    Biochem Biophys Res Commun 286:587-94. 2001
    ..Further analysis demonstrates that although Tat alone lacks direct effect on IkappaBalpha degradation or dissociation from NF-kappaB, Tat can substantially enhance the capacity of NF-kappaB-inducing ..
  9. doi HIV-1 Tat dysregulation of lipopolysaccharide-induced cytokine responses: microbial interactions in HIV infection
    Howard C H Yim
    Cytokine Biology Group, Department of Paediatrics and Adolescent Medicine, China bBio Screening Unit, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong Special Administrative Region, China
    AIDS 23:1473-84. 2009
    ..To examine whether the HIV-1 Tat protein impairs the lipopolysaccharide (LPS)-induced cytokine responses...
  10. pmc HIV replication in CD4+ T lymphocytes in the presence and absence of follicular dendritic cells: inhibition of replication mediated by α-1-antitrypsin through altered IκBα ubiquitination
    Xueyuan Zhou
    Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, USA
    J Immunol 186:3148-55. 2011
    ....
  11. doi The ins and outs of HIV-1 Tat
    Solène Debaisieux
    CPBS, UMR 5236 CNRS, Universite de Montpellier, 1919 Route de Mende, 34923, Montpellier Cedex 05, France
    Traffic 13:355-63. 2012
    ..This review focuses on some of the recently identified molecular details underlying the unusual transcellular transport pathway used by Tat, such as the role of the single Trp in Tat for its membrane insertion and translocation...
  12. pmc 3-Hydroxyanthranilic acid inhibits PDK1 activation and suppresses experimental asthma by inducing T cell apoptosis
    Tomoko Hayashi
    Department of Medicine, University of California at San Diego, La Jolla, CA 92093 0663, USA
    Proc Natl Acad Sci U S A 104:18619-24. 2007
    ..Thus, HAA is a natural inhibitor that restrains T cell expansion and activation...
  13. ncbi Down syndrome candidate region 1 increases the stability of the IkappaBalpha protein: implications for its anti-inflammatory effects
    Young Sun Kim
    Department of Pharmacology, Catholic University of Korea, Seoul 137 701, Korea
    J Biol Chem 281:39051-61. 2006
    ..DSCR1.4 did not affect the PMA-stimulated phosphorylation or degradation kinetics of IkappaBalpha; however, DSCR1...
  14. pmc HIV-1-mediated apoptosis of neuronal cells: Proximal molecular mechanisms of HIV-1-induced encephalopathy
    Yan Xu
    Dorrance H Hamilton Laboratories, Center for Human Virology and Biodefense, Division of Infectious Diseases and Environmental Medicine, Department of Medicine, Thomas Jefferson University, 1020 Locust Street, Suite 329, Philadelphia, PA 19107, USA
    Proc Natl Acad Sci U S A 101:7070-5. 2004
    ..These analyses suggest molecular mechanisms for the induction of apoptosis relating to the exposure of viral and host cell factors and rationally designed approaches toward neuroprotection...
  15. doi Glycogen synthase kinase-3β is a crucial mediator of signal-induced RelB degradation
    M Neumann
    Department of Molecular Pathology, Institute for Pathology, University Hospital, Eberhard Karls University, Tuebingen, Germany
    Oncogene 30:2485-92. 2011
    ..The serine residue 552 is a target of GSK-3β-mediated phosphorylation in vitro and in vivo. We conclude that GSK-3β is a crucial regulator of RelB degradation, stressing the relevant linkage between the NF-κB system and GSK-3β...
  16. ncbi Association between HTLV-1 Tax and I kappa B alpha is dependent on the I kappa B alpha phosphorylation state
    L Petropoulos
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, Montreal, Quebec, Canada
    Virology 252:189-99. 1998
    ..B/I kappa B regulatory proteins, we examined the significance of an in vivo association between Tax and the I kappa B alpha inhibitor...
  17. ncbi Extracellular HIV type 1 Tat protein induces CD69 expression through NF-kappaB activation: possible correlation with cell surface Tat-binding proteins
    M V Blazquez
    Departamento de Fisiología e Immunología, Universidad de Cordoba, Cordoba, Spain
    AIDS Res Hum Retroviruses 15:1209-18. 1999
    ..Tat induces NF-kappaB binding to DNA as a result of IkappaBalpha phosphorylation and degradation, which depend on the intracellular redox state...
  18. pmc Nedd8 modification of cul-1 activates SCF(beta(TrCP))-dependent ubiquitination of IkappaBalpha
    M A Read
    LeukoSite, Inc, Cambridge, Massachusetts 02139, USA
    Mol Cell Biol 20:2326-33. 2000
    Regulation of NF-kappaB occurs through phosphorylation-dependent ubiquitination of IkappaBalpha, which is degraded by the 26S proteasome...
  19. doi Inhibitor IkappaBalpha promoter functional polymorphisms in patients with rheumatoid arthritis
    Ruei Nian Li
    Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan
    J Clin Immunol 30:676-80. 2010
    ..Many proinflammatory cytokines are involved in the inflammatory process of RA. IkappaBalpha conjugates with NF-kappaB and is a key player in regulation of the inflammatory process...
  20. ncbi Phosphorylation of RelA/p65 on serine 536 defines an I{kappa}B{alpha}-independent NF-{kappa}B pathway
    Carl Y Sasaki
    Laboratory of Immunology, NIA, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Biol Chem 280:34538-47. 2005
    The association of the NF-kappaB p65/p50 dimer with IkappaBalpha plays a pivotal role in regulating its nuclear translocation and gene transcription...
  21. ncbi Suppression of NF-kappaB and NF-kappaB-regulated gene expression by sulforaphane and PEITC through IkappaBalpha, IKK pathway in human prostate cancer PC-3 cells
    Changjiang Xu
    Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
    Oncogene 24:4486-95. 2005
    ..To further elucidate the mechanism, we utilized the dominant-negative mutant of inhibitor of NF-kappaB alpha (IkappaBalpha) (SR-IkappaBalpha)...
  22. pmc Interleukin (IL) 1beta induction of IL-6 is mediated by a novel phosphatidylinositol 3-kinase-dependent AKT/IkappaB kinase alpha pathway targeting activator protein-1
    Catherine M Cahill
    Neurochemistry Laboratory, Department of Psychiatry Neuroscience and Genetics and Aging Research Unit, Massachusetts General Hospital East, Charlestown, Massachusetts 02129, USA
    J Biol Chem 283:25900-12. 2008
    ..Neither inhibition of PI 3-kinase/AKT nor IKKalphaT23A overexpression affected IkappaBalpha degradation in response to IL-1...
  23. pmc Caspase-3-mediated cleavage of p65/RelA results in a carboxy-terminal fragment that inhibits IkappaBalpha and enhances HIV-1 replication in human T lymphocytes
    Mayte Coiras
    AIDS Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain
    Retrovirology 5:109. 2008
    ..Its major inhibitor IkappaBalpha constitutes a master terminator of NF-kappaB response that is complemented by degradation of p65/RelA.
  24. pmc Variant in the 3' region of the IkappaBalpha gene associated with insulin resistance in Hispanic Americans: The IRAS Family Study
    Melissa R Miller
    Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, Aurora, Colorado, USA
    Obesity (Silver Spring) 18:555-62. 2010
    ..We hypothesized that one or more variants in the IkappaBalpha gene (NFKBIA) or surrounding untranslated regions would be associated with insulin sensitivity (S(I)) in ..
  25. doi The PPE18 protein of Mycobacterium tuberculosis inhibits NF-κB/rel-mediated proinflammatory cytokine production by upregulating and phosphorylating suppressor of cytokine signaling 3 protein
    Shiny Nair
    Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad 500001, Andhra Pradesh, India
    J Immunol 186:5413-24. 2011
    ..Also, this study highlights the possible mechanisms by which the M. tuberculosis suppresses production of proinflammatory cytokines using PPE18...
  26. pmc Transdominant mutants of I kappa B alpha block Tat-tumor necrosis factor synergistic activation of human immunodeficiency virus type 1 gene expression and virus multiplication
    P Beauparlant
    Lady Davis Institute for Medical Research, Montreal, Quebec, Canada
    J Virol 70:5777-85. 1996
    ..In the present study, we examined the effect of transdominant mutants of I kappa B alpha on the synergistic activation of the HIV-1 LTR by TNF-alpha and the HIV-1 transactivator, Tat, in Jurkat T ..
  27. ncbi HIV-1 Vpr suppresses immune activation and apoptosis through regulation of nuclear factor kappa B
    V Ayyavoo
    Department of Pathology, University of Pennsylvania, Philadelphia 19104, USA
    Nat Med 3:1117-23. 1997
    ..The effects of Vpr could be reversed by RU486. Our finding that Vpr can regulate NF-kappa B supports the hypothesis that some aspects of viral pathogenesis are the consequence of cell dysregulation by Vpr...
  28. pmc The human immunodeficiency virus type 1 accessory protein Vpu induces apoptosis by suppressing the nuclear factor kappaB-dependent expression of antiapoptotic factors
    H Akari
    Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Exp Med 194:1299-311. 2001
    ..Thus, Vpu induces apoptosis through activation of the caspase pathway by way of inhibiting the NF-kappaB-dependent expression of antiapoptotic genes...
  29. pmc Directed expression of the HIV-1 accessory protein Vpu in Drosophila fat-body cells inhibits Toll-dependent immune responses
    François Leulier
    Centre de Génétique Moléculaire Centre National de la Recherche Scientifique, Batiment 26, Avenue de la Terrasse, 91198 Gif sur Yvette, France
    EMBO Rep 4:976-81. 2003
    ....
  30. ncbi HIV-1 Vpr and anti-inflammatory activity
    Karuppiah Muthumani
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    DNA Cell Biol 23:239-47. 2004
    ..These activities are worthy of further examination for control of hyperinflammatory and hyperproliferative conditions...
  31. pmc Molecular mechanism of hTid-1, the human homolog of Drosophila tumor suppressor l(2)Tid, in the regulation of NF-kappaB activity and suppression of tumor growth
    Hua Cheng
    Department of Cancer Biology, University of Texas M D Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
    Mol Cell Biol 25:44-59. 2005
    ..strongly associated with the cytoplasmic protein complex of NF-kappaB-IkappaB through direct interaction with IkappaBalpha/beta and the IKKalpha/beta subunits of the IkappaB kinase complex...
  32. ncbi HIV-1 viral protein R (Vpr) & host cellular responses
    Richard Yuqi Zhao
    Department of Pathology, University of Maryland School of Medicine, 10 South Pine Street, MSTF 600, Baltimore, MD 21201, USA
    Indian J Med Res 121:270-86. 2005
    ..Strategies with potential application for future antiviral therapies directed at suppressing Vpr activities are described...
  33. ncbi FBI-1 enhances transcription of the nuclear factor-kappaB (NF-kappaB)-responsive E-selectin gene by nuclear localization of the p65 subunit of NF-kappaB
    Dong Kee Lee
    Department of Biochemistry and Molecular Biology and the Institute of Genetic Sciences, BK21 Project for Medical Sciences, Yonsei University School of Medicine, 134 Shinchon dong, Seodaemoon ku, Seoul 120 752, Korea
    J Biol Chem 280:27783-91. 2005
    ..FBI-1 also interacted with IkappaB alpha and IkappaB beta...
  34. pmc Nox2 and Rac1 regulate H2O2-dependent recruitment of TRAF6 to endosomal interleukin-1 receptor complexes
    Qiang Li
    Department of Anatomy and Cell Biology, College of Medicine, University of Iowa, 51 Newton Road, Iowa City, IA 52242, USA
    Mol Cell Biol 26:140-54. 2006
    ..The identification of Nox-active endosomes helps explain how subcellular compartmentalization of redox signals can be used to direct receptor activation from the plasma membrane...
  35. pmc An alternative splice product of IkappaB kinase (IKKgamma), IKKgamma-delta, differentially mediates cytokine and human T-cell leukemia virus type 1 tax-induced NF-kappaB activation
    Tao Hai
    Department of Internal Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston, Texas 77555 1060, USA
    J Virol 80:4227-41. 2006
    ..Differing levels of IKKgamma-delta expression, therefore, may affect signal transduction cascades coupling to IKK...
  36. pmc Regulation of I(kappa)B kinase complex by phosphorylation of (gamma)-binding domain of I(kappa)B kinase (beta) by Polo-like kinase 1
    Tomoyasu Higashimoto
    Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90089 9176, USA
    J Biol Chem 283:35354-67. 2008
    ..tumor necrosis factor (TNF)-induced IKK activation, resulting in decreased phosphorylation of endogenous IkappaBalpha and reduced NF-kappaB activation...
  37. doi Inhibitor of nuclear factor-kappaB alpha derepresses hypoxia-inducible factor-1 during moderate hypoxia by sequestering factor inhibiting hypoxia-inducible factor from hypoxia-inducible factor 1alpha
    Dong Hoon Shin
    Department of Pharmacology Ischemic Hypoxic Disease Institute, Seoul National University College of Medicine, Korea
    FEBS J 276:3470-80. 2009
    ..Therefore, IkappaB alpha, owing to its interactions with NF-kappaB and HIF-1alpha, may play a pivotal role in the crosstalk between the molecular events that underlie inflammatory and hypoxic responses...
  38. pmc Aurora-A down-regulates IkappaBalpha via Akt activation and interacts with insulin-like growth factor-1 induced phosphatidylinositol 3-kinase pathway for cancer cell survival
    Jin E Yao
    State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat Sen University, 651 Dongfeng Road East, Guangzhou, PR China
    Mol Cancer 8:95. 2009
    ..As a bona fide oncoprotein, Aurora-A aberrant overexpression leads to oncogenic transformation. Yet, the mechanisms by which Aurora-A enhances cancer cell survival remain to be elucidated...
  39. pmc I kappa B/MAD-3 masks the nuclear localization signal of NF-kappa B p65 and requires the transactivation domain to inhibit NF-kappa B p65 DNA binding
    P A Ganchi
    Gladstone Institute of Virology and Immunology, University of California, San Francisco
    Mol Biol Cell 3:1339-52. 1992
    ..However, no loss of DNA binding activity is observed, presumably reflecting the unique C-terminal domain that is distinct from that present in NF-kappa B p65...
  40. pmc Nuclear uptake control of NF-kappa B by MAD-3, an I kappa B protein present in the nucleus
    U Zabel
    Laboratory for Molecular Biology, Ludwig Maximilians University, Munich, Martinsried, Germany
    EMBO J 12:201-11. 1993
    ....
  41. pmc Involvement of regulatory and catalytic subunits of phosphoinositide 3-kinase in NF-kappaB activation
    C Beraud
    Tularik, Two Corporate Drive, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 96:429-34. 1999
    ..Our data suggest that both the regulatory and the catalytic subunit of PI3-kinase play a role in NF-kappaB activation by the tyrosine phosphorylation-dependent pathway...
  42. ncbi Mitogen-activated protein kinase/ERK kinase kinases 2 and 3 activate nuclear factor-kappaB through IkappaB kinase-alpha and IkappaB kinase-beta
    Q Zhao
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 274:8355-8. 1999
    ..We now show that MEKK2 and MEKK3 can in vivo activate IKK-alpha and IKK-beta, induce site-specific IkappaBalpha phosphorylation, and, relatively modestly, activate an NF-kappaB reporter gene...
  43. ncbi The Bcl-3 oncoprotein acts as a bridging factor between NF-kappaB/Rel and nuclear co-regulators
    R Dechend
    Max Delbrück Center for Molecular Medicine MDC, Berlin
    Oncogene 18:3316-23. 1999
    ..These data implicate Bcl-3 as an adaptor between NF-kappaB p50/p52 and other transcription regulators and suggest that its gene activation function may at least in part be due to recruitment of the Tip60 histone actetylase...
  44. ncbi Chromosomal localization of the genes encoding the p50/p105 subunits of NF-kappa B (NFKB2) and the I kappa B/MAD-3 (NFKBI) inhibitor of NF-kappa B to 4q24 and 14q13, respectively
    M M Le Beau
    Section of Hematology Oncology, University of Chicago, Illinois 60637
    Genomics 14:529-31. 1992
    ..Recently the genes encoding the p50 and p65 subunits of NF-kappa B, as well as one form of I kappa B/MAD-3 (NFKBI), have been cloned...
  45. ncbi Direct phosphorylation of IkappaB by IKKalpha and IKKbeta: discrimination between free and NF-kappaB-bound substrate
    E Zandi
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
    Science 281:1360-3. 1998
    ..This result explains how free IkappaB can accumulate in cells in which IKK is still active and thus can contribute to the termination of NF-kappaB activation...
  46. pmc Clonal deleterious mutations in the IkappaBalpha gene in the malignant cells in Hodgkin's lymphoma
    B Jungnickel
    Institute for Genetics, University of Cologne, 50931 Cologne, Germany
    J Exp Med 191:395-402. 2000
    ..cells micromanipulated from histological sections of HL, we detect clonal deleterious somatic mutations in the IkappaBalpha gene in two of three Epstein-Barr virus (EBV)-negative cases but not in two EBV-positive cases (in which a ..
  47. ncbi Inhibitor kappa B-alpha (IkappaB-alpha) promoter polymorphisms in UK and Dutch sarcoidosis
    A Abdallah
    Clinical Genomics Group, Royal Brompton Hospital, Imperial College, London, UK
    Genes Immun 4:450-4. 2003
    ..01). The -826T allelic carriage did not show any association with lung function. These results indicate that the NF-kappaB activation pathway might be associated with the inflammation of sarcoidosis...
  48. ncbi A polymorphism of the NFKBIA gene is associated with Crohn's disease patients lacking a predisposing allele of the CARD15 gene
    Wolfram Klein
    Abteilung für Humangenetik, Ruhr Universitat, Bochum, Germany
    Int J Colorectal Dis 19:153-6. 2004
    ..Nuclear factor kappa-B (NFkappaB) plays a crucial role in diseases associated with dysregulated immune response. NFkappaB inhibitor alpha downregulates the activity of NFkappaB...
  49. ncbi Tyrosine nitration on p65: a novel mechanism to rapidly inactivate nuclear factor-kappaB
    Sung Wook Park
    Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
    Mol Cell Proteomics 4:300-9. 2005
    ..Tyr nitration of p65 induced its dissociation from p50, its association with IkappaBalpha, and subsequent sequestration of p65 in the cytoplasm by IkappaBalpha-mediated export...
  50. ncbi IkappaBalpha promoter polymorphisms in patients with rheumatoid arthritis
    C H Lin
    Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Taiwan
    Int J Immunogenet 34:51-4. 2007
    ..The IkappaBalpha promoter polymorphisms were determined using the polymerase chain reaction/restriction fragment length ..
  51. pmc Pre-folding IkappaBalpha alters control of NF-kappaB signaling
    Stephanie M E Truhlar
    Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0378, USA
    J Mol Biol 380:67-82. 2008
    ..b>IkappaBalpha binds to and inhibits the transcriptional activity of NF-kappaB via its ankyrin repeat (AR) domain...
  52. pmc Polymorphisms in NF-kappaB inhibitors and risk of epithelial ovarian cancer
    Kristin L White
    Mayo Clinic College of Medicine, Rochester, MN, USA
    BMC Cancer 9:170. 2009
    ..Inhibitors of kappaB (IkappaB) prevent NF-kappaB activation by sequestering NF-kappaB proteins in the cytoplasm until IkappaB proteins are phosphorylated and degraded...
  53. doi Mutations of NFKBIA, encoding IkappaB alpha, are a recurrent finding in classical Hodgkin lymphoma but are not a unifying feature of non-EBV-associated cases
    Annette Lake
    LRF Virus Centre, Institute of Comparative Medicine, University of Glasgow, Glasgow, United Kingdom
    Int J Cancer 125:1334-42. 2009
    ..It remains possible that defects in genes encoding other inhibitors of NF-kappaB, such as TNFAIP3 (A20) and CYLD, are involved in the latter cases, as described for one case in this series...
  54. pmc IkappaBalpha gene promoter polymorphisms are associated with hepatocarcinogenesis in patients infected with hepatitis B virus genotype C
    Yongchao He
    Department of Epidemiology, The 1st Affiliated Hospital, Second Military Medical University, Shanghai 200433, People s Republic of China
    Carcinogenesis 30:1916-22. 2009
    ..associations of the polymorphisms within the promoter regions of NFKB1 encoding NF-kappaB1 and NFKBIA encoding IkappaBalpha with the development of HCC...
  55. pmc IkappaBalpha polymorphism at promoter region (rs2233408) influences the susceptibility of gastric cancer in Chinese
    Shiyan Wang
    Institute of Digestive Disease and Department of Meddicine and Therapeutics, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China
    BMC Gastroenterol 10:15. 2010
    ....
  56. pmc Proteasome inhibitor PS-341 (bortezomib) induces calpain-dependent IkappaB(alpha) degradation
    Chunyang Li
    Department of Hematology and Medical Oncology, Emory University School of Medicine and Winship Cancer Institute, Atlanta, Georgia 30322, USA
    J Biol Chem 285:16096-104. 2010
    ..Collectively, these unexpected findings suggest not only a novel paradigm regarding the relationship between proteasome inhibition and NF-kappaB activity but also a strategy to enhance the anticancer efficacy of PS-341...
  57. ncbi Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity
    S Haskill
    Lineberger Comprehensive Cancer Center, Department of Obstetrics and Gynecology, University of North Carolina, Chapel Hill 27599
    Cell 65:1281-9. 1991
    ..The MAD-3 cDNA encodes an I kappa B-like protein that is likely to be involved in regulation of transcriptional responses to NF-kappa B, including adhesion-dependent pathways of monocyte activation...
  58. ncbi I kappa B: a specific inhibitor of the NF-kappa B transcription factor
    P A Baeuerle
    Whitehead Institute for Biomedical Research, MA 02142
    Science 242:540-6. 1988
    ..The data show the existence of a phorbol ester-responsive regulatory protein that acts by controlling the DNA binding activity and subcellular localization of a transcription factor...
  59. pmc Signal-induced degradation of I kappa B alpha requires site-specific ubiquitination
    D C Scherer
    Department of Microbiology and Immunology, Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    Proc Natl Acad Sci U S A 92:11259-63. 1995
    The inhibitor protein I kappa B alpha controls the nuclear import of the transcription factor NF-kappa B. The inhibitory activity of I kappa B alpha is regulated from the cytoplasmic compartment by signal-induced proteolysis...
  60. pmc Regulation of human immunodeficiency virus type 1 and cytokine gene expression in myeloid cells by NF-kappa B/Rel transcription factors
    A Roulston
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Sir Mortimer B Davis Jewish General Hospital, Montreal, Quebec, Canada
    Microbiol Rev 59:481-505. 1995
    ..Phosphorylation and degradation of the cytoplasmic inhibitor I kappa B alpha are crucial regulatory events in the activation of NF-kappa B DNA-binding activity...
  61. ncbi Signal-induced site-specific phosphorylation targets I kappa B alpha to the ubiquitin-proteasome pathway
    Z Chen
    Myogenics, Inc, Cambridge, Massachusetts 02139, USA
    Genes Dev 9:1586-97. 1995
    The transcription factor NF-kappa B is sequestered in the cytoplasm by the inhibitor protein I kappa B alpha. Extracellular inducers of NF-kappa B activate signal transduction pathways that result in the phosphorylation and subsequent ..
  62. pmc Inducible nuclear expression of newly synthesized I kappa B alpha negatively regulates DNA-binding and transcriptional activities of NF-kappa B
    F Arenzana-Seisdedos
    School of Biological and Medical Sciences, University of St Andrews, Scotland
    Mol Cell Biol 15:2689-96. 1995
    ..The inhibitor protein I kappa B alpha maintains NF-kappa B in an inactive form in the cytoplasms of unstimulated cells, but upon cell activation, I ..
  63. pmc Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation
    J A Brockman
    Howard Hughes Medical Institute, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0295, USA
    Mol Cell Biol 15:2809-18. 1995
    ..activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-..
  64. pmc Domain organization of I kappa B alpha and sites of interaction with NF-kappa B p65
    E Jaffray
    School of Biological and Medical Sciences, University of St Andrews, Fife, Scotland
    Mol Cell Biol 15:2166-72. 1995
    ..and cellular distribution of the transcription factor NF-kappa B are regulated by the inhibitor protein I kappa B alpha. I kappa B alpha belongs to a family of proteins that contain multiple repeats of a 30- to 35-amino-acid ..
  65. ncbi Site-specific phosphorylation of IkappaBalpha by a novel ubiquitination-dependent protein kinase activity
    Z J Chen
    ProScript Incorporated, Cambridge, Massachusetts, 02139, USA
    Cell 84:853-62. 1996
    ..activation of the transcription factor NF-kappaB requires specific phosphorylation of the inhibitor IkappaBalpha and its subsequent proteolytic degradation...
  66. ncbi Role of IkappaBalpha ubiquitination in signal-induced activation of NFkappaB in vivo
    M Roff
    School of Biological and Medical Sciences, University of St Andrews, Fife, Scotland
    J Biol Chem 271:7844-50. 1996
    ..the transcription factor NF-kappaB is held in the cytoplasm in an inactive state by the inhibitor protein IkappaBalpha. Stimulation of cells results in rapid phosphorylation and degradation of IkappaBalpha, thus releasing NF-..
  67. pmc Mapping of the inducible IkappaB phosphorylation sites that signal its ubiquitination and degradation
    J Didonato
    Department of Pharmacology, Program in Biomedical Science, University of California, San Diego School of Medicine, La Jolla, USA
    Mol Cell Biol 16:1295-304. 1996
    Extracellular stimuli that activate the transcription factor NF-kappaB cause rapid phosphorylation of the IkappaBalpha inhibitor, which retains NF-kappaB in the cytoplasm of nonstimulated cells...
  68. ncbi Tyrosine phosphorylation of I kappa B-alpha activates NF-kappa B without proteolytic degradation of I kappa B-alpha
    V Imbert
    Inserm Unité 364 Faculté de Médecine Pasteur, Nice, France
    Cell 86:787-98. 1996
    ..Tyrosine phosphorylation of I kappa B-alpha represents a proteolysis-independent mechanism of NF-kappa B activation that directly couples NF-kappa B to cellular tyrosine kinase...
  69. ncbi A cytokine-responsive IkappaB kinase that activates the transcription factor NF-kappaB
    J A DiDonato
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California at San Diego, La Jolla 92093 0636, USA
    Nature 388:548-54. 1997
    ..A component of IKK was molecularly cloned and identified as a serine kinase. IKK turns out to be the long-sought-after protein kinase that mediates the critical regulatory step in NF-kappaB activation...
  70. ncbi IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK
    J D Woronicz
    Tularik, Two Corporate Drive, South San Francisco, CA 94080, USA
    Science 278:866-9. 1997
    ..Overexpression of a catalytically inactive form of IKK-beta blocked cytokine-induced NF-kappaB activation. Thus, an active IkappaB kinase complex may require three distinct protein kinases...
  71. pmc I kappaB alpha physically interacts with a cytoskeleton-associated protein through its signal response domain
    P Crepieux
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, Department of Medicine, McGill University, Montreal, Que, Canada
    Mol Cell Biol 17:7375-85. 1997
    ....
  72. ncbi SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation
    J M Desterro
    School of Biomedical Science, University of St Andrews, Fife, United Kingdom
    Mol Cell 2:233-9. 1998
    Activation of NF-kappaB is achieved by ubiquitination and proteasome-mediated degradation of IkappaBalpha. We have detected modified IkappaBalpha, conjugated to the small ubiquitin-like protein SUMO-1, which is resistant to signal-induced ..
  73. ncbi Structure of an IkappaBalpha/NF-kappaB complex
    M D Jacobs
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA
    Cell 95:749-58. 1998
    The inhibitory protein, IkappaBalpha, sequesters the transcription factor, NF-kappaB, as an inactive complex in the cytoplasm...
  74. ncbi The crystal structure of the IkappaBalpha/NF-kappaB complex reveals mechanisms of NF-kappaB inactivation
    T Huxford
    Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093 0359, USA
    Cell 95:759-70. 1998
    b>IkappaBalpha regulates the transcription factor NF-kappaB through the formation of stable IkappaBalpha/NF-kappaB complexes...
  75. ncbi Nuclear retention of IkappaBalpha protects it from signal-induced degradation and inhibits nuclear factor kappaB transcriptional activation
    M S Rodriguez
    Institute of Biomolecular Sciences, School of Biomedical Sciences, University of St Andrews, The North Haugh, St Andrews KY16 9TS, Scotland, United Kingdom
    J Biol Chem 274:9108-15. 1999
    ..factor kappaB (NF-kappaB) is mediated by signal-induced phosphorylation and degradation of its inhibitor, IkappaBalpha. However, NF-kappaB activation induces rapid resynthesis of IkappaBalpha, which is responsible for post-..
  76. ncbi The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway
    J Ninomiya-Tsuji
    Department of Molecular Biology, Graduate School of Science, Nagoya University, and CREST, Japan Science and Technology Corporation
    Nature 398:252-6. 1999
    ..Activated TAK1 phosphorylates NIK, which stimulates IKK-alpha activity. Our results indicate that TAK1 links TRAF6 to the NIK-IKK cascade in the IL-1 signalling pathway...
  77. ncbi Expression of IkappaBalpha in the nucleus of human peripheral blood T lymphocytes
    T Lain de Lera
    Servicio de Microbiologia, Centro de Investigacion, Hospital 12 de Octubre, Madrid, Spain
    Oncogene 18:1581-8. 1999
    ..Our results demonstrate that in resting and PMA-activated human PBL, I(kappa)B(alpha) is present in the nucleus in an apparently inactive form unable to disrupt NF-kappaB binding from DNA...
  78. ncbi Serine 32 and serine 36 of IkappaBalpha are directly phosphorylated by protein kinase CKII in vitro
    J A Taylor
    Department of Immunology, Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55905, USA
    J Mol Biol 290:839-50. 1999
    b>IkappaBalpha is an inherently unstable protein which binds to and retains the ubiquitous transcription factor NFkappaB in the cytoplasm of resting cells...
  79. ncbi The human immunodeficiency virus type 1 Vpu protein inhibits NF-kappa B activation by interfering with beta TrCP-mediated degradation of Ikappa B
    S Bour
    Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892 0460, USA
    J Biol Chem 276:15920-8. 2001
    ..However, in the presence of Vpu, this HIV-mediated NF-kappaB activation was markedly reduced. These results suggest that Vpu modulates both virus- and cytokine-induced activation of NF-kappaB in HIV-1-infected cells...
  80. ncbi Duration of nuclear NF-kappaB action regulated by reversible acetylation
    - Chen Lf
    Gladstone Institute of Virology and Immunology, Department of Medicine, University of California, San Francisco, CA 94141, USA
    Science 293:1653-7. 2001
    ..regulate the termination of nuclear NF-kappaB action remain poorly defined, although the activation of de novo IkappaBalpha gene expression by NF-kappaB likely plays a key role...
  81. ncbi NF-kappaB activation upon interaction of HIV-1 envelope glycoproteins with cell surface CD4 involves IkappaB kinases
    Guillaume Bossis
    Laboratoire Infections Retrovirales et Signalisation Cellulaire, CNRS UMR 5121, Institut de Biologie, 4 Bd Henri IV, 34060, Montpellier, France
    FEBS Lett 516:257-64. 2002
    ..Taken together, these results confirm that IKKs complex play a key role in gp120(env)-induced NF-kappaB activation...
  82. ncbi Identification of polymorphisms of the IkappaBalpha gene associated with an increased risk of multiple myeloma
    Kimberly M Parker
    Division of Hematology and Oncology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA
    Cancer Genet Cytogenet 137:43-8. 2002
    When NF-kappaB proteins are bound to IkappaBalpha, they remain in the cytosol, and are unable to act as transcription factors...
  83. ncbi Polymorphic variants of NFKB1 and its inhibitory protein NFKBIA, and their involvement in sporadic breast cancer
    Joanne E Curran
    Genomics Research Centre and Wesley Research Institute, School of Health Science, Griffith University Gold Coast, Parklands Drive, 9726, Southport, QLD, Australia
    Cancer Lett 188:103-7. 2002
    ..Results do not support an involvement of the tested NFKB1 and NFKBIA polymorphisms in susceptibility to sporadic breast cancer, in the tested Caucasian population...
  84. ncbi Post-activation turn-off of NF-kappa B-dependent transcription is regulated by acetylation of p65
    Rosemary Kiernan
    Laboratoire de Virologie Moleculaire, Institut de Genetique Humaine, Montpellier 34296, France
    J Biol Chem 278:2758-66. 2003
    ..localization and consequently the transcriptional activity of NF-kappaB is tightly regulated by its partner IkappaBalpha. Here, we show that the p65 subunit of NF-kappaB is acetylated by both p300 and PCAF on lysines 122 and 123...
  85. ncbi Tyrosine phosphorylation of I kappa B alpha activates NF kappa B through a redox-regulated and c-Src-dependent mechanism following hypoxia/reoxygenation
    Chenguang Fan
    Molecular Biology Graduate Program, The Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa 52242, USA
    J Biol Chem 278:2072-80. 2003
    ..Tyrosine 42 phosphorylation of I kappa B alpha has been shown to mediate NF kappa B activation following hypoxia/reoxygenation (H/R) or pervanadate ..
  86. ncbi Syk, a protein-tyrosine kinase, suppresses the cell motility and nuclear factor kappa B-mediated secretion of urokinase type plasminogen activator by inhibiting the phosphatidylinositol 3'-kinase activity in breast cancer cells
    Ganapati H Mahabeleshwar
    National Centre for Cell Science NCCS, NCCS Complex, Pune 411 007, India
    J Biol Chem 278:6209-21. 2003
    ..PI 3'-kinase activity and stimulated the interaction between the inhibitor of nuclear factor kappa B alpha (I kappa B alpha) and the p85 alpha domain of PI 3'-kinase through tyrosine phosphorylation of the I kappa B alpha, which ..
  87. pmc betaTrCP-mediated proteolysis of NF-kappaB1 p105 requires phosphorylation of p105 serines 927 and 932
    Valerie Lang
    Division of Immune Cell Biology, National Institute for Medical Research, London NW7 1AA, United Kingdom
    Mol Cell Biol 23:402-13. 2003
    ..resides in a conserved motif (Asp-Ser(927)-Gly-Val-Glu-Thr-Ser(932)) homologous to the IKK target sequence in IkappaBalpha. In this study, TNF-alpha-induced p105 proteolysis was revealed to additionally require the phosphorylation of ..
  88. ncbi Cytoplasmic IkappaBalpha increases NF-kappaB-independent transcription through binding to histone deacetylase (HDAC) 1 and HDAC3
    Patrick Viatour
    Laboratory of Medical Chemistry and Human Genetics, Center for Cellular and Molecular Therapy, University of Liege, Sart Tillman, 4000 Liege, Belgium
    J Biol Chem 278:46541-8. 2003
    b>IkappaBalpha is an inhibitory molecule that sequesters NF-kappaB dimers in the cytoplasm of unstimulated cells. Upon stimulation, NF-kappaB moves to the nucleus and induces the expression of a variety of genes including IkappaBalpha...
  89. pmc A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency
    Gilles Courtois
    Unité de Biologie Moléculaire de l Expression Génique, Centre National de la Recherche Scientifique URA 2582, Institut Pasteur, Paris, France
    J Clin Invest 112:1108-15. 2003
    ..an autosomal-dominant (AD) form of EDA-ID associated with a heterozygous missense mutation at serine 32 of IkappaBalpha. This mutation is gain-of-function, as it enhances the inhibitory capacity of IkappaBalpha by preventing its ..
  90. ncbi Identification of variants in NFKBIA and association analysis with hepatocellular carcinoma risk among chronic HBV patients
    Lyoung Hyo Kim
    Department of Genetic Epidemiology, SNP Genetics, Inc, 11th Floor, MaeHun B D, 13 Chongro 4 Ga, Chongro Gu, Seoul, Korea
    Hum Mutat 21:652-3. 2003
    Human nuclear factor of kappa light chain gene enhancer in B cells inhibitor, alpha (NFKBIA) inhibits the action of NF-kappaB by forming a heterodimer with NF-kappaB, and preventing its translocation to the nucleus...
  91. pmc Recruitment of IkappaBalpha to the hes1 promoter is associated with transcriptional repression
    Cristina Aguilera
    Centre Oncologia Molecular, Institut d Investigació Biomèdica de Bellvitge Institut de Recerca Oncologica, Barcelona 08907, Spain
    Proc Natl Acad Sci U S A 101:16537-42. 2004
    ..Nevertheless, a nuclear fraction of IkappaBalpha has consistently been detected and associated with repression of nuclear NF-kappaB...
  92. ncbi Germline mutations and polymorphisms in the NFKBIA gene in Hodgkin lymphoma
    Julie Osborne
    LRF Virus Centre, Institute of Comparative Medicine, University of Glasgow, Glasgow, United Kingdom
    Int J Cancer 116:646-51. 2005
    Somatic inactivation of NFKBIA, the gene encoding IkappaBalpha, is a frequent occurrence in the malignant Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin lymphoma (HL)...
  93. ncbi Haplotypic structure across the I kappa B alpha gene (NFKBIA) and association with multiple myeloma
    Charlotte F Spink
    Department of Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, UK
    Cancer Lett 246:92-9. 2007
    ..The NFKBIA gene product, IkappaBalpha, binds to NF-kappaB preventing its activation and is important in mediating resistance to apoptosis in B-cell ..
  94. pmc Thermodynamics reveal that helix four in the NLS of NF-kappaB p65 anchors IkappaBalpha, forming a very stable complex
    Simon Bergqvist
    Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0378, USA
    J Mol Biol 360:421-34. 2006
    b>IkappaBalpha is an ankyrin repeat protein that inhibits NF-kappaB transcriptional activity by sequestering NF-kappaB outside of the nucleus in resting cells...
  95. pmc Regions of IkappaBalpha that are critical for its inhibition of NF-kappaB.DNA interaction fold upon binding to NF-kappaB
    Stephanie M E Truhlar
    Department of Chemistry and Biochemistry, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0378, USA
    Proc Natl Acad Sci U S A 103:18951-6. 2006
    ..b>IkappaBalpha, -beta, and -epsilon bind to NF-kappaBs and inhibit their transcriptional activity...
  96. ncbi Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations
    Jingfang Gao
    Department of Oncology, Institute of Biomedicine and Surgery, Linkoping University, Linkoping, Sweden
    Scand J Gastroenterol 42:345-50. 2007
    ..study was to investigate the susceptibility of an A to G variation (rs696) in the 3' UTR of NFKBIA (encoding IkappaBalpha) to colorectal cancer (CRC) and the association of this polymorphism with clinicopathologic variables in CRC ..
  97. ncbi Importance of polymorphisms in NF-kappaB1 and NF-kappaBIalpha genes for melanoma risk, clinicopathological features and tumor progression in Swedish melanoma patients
    Huajie Bu
    Department of Dermatology, Institute of Biomedicine and Surgery, Linkoping University, 581 85, Linkoping, Sweden
    J Cancer Res Clin Oncol 133:859-66. 2007
    ..Importance of polymorphisms in NF-kappaB1 and NF-kappaBIalpha genes for melanoma risk, clinicopathological features and tumor progression is analyzed in Swedish melanoma patients...
  98. ncbi IkappaB-alpha represses the transcriptional activity of the HIV-1 Tat transactivator by promoting its nuclear export
    Antimina Puca
    Department of Biochemistry and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
    J Biol Chem 282:37146-57. 2007
    ..This novel mechanism of cross-talk between Tat and IkappaB-alpha provides further insights into the mechanisms of HIV-1 regulation and could assist in the development of novel strategies for AIDS therapy...
  99. ncbi RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1alpha during hypoxia
    Alberto Carbia-Nagashima
    Departamento de Fisiología y Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
    Cell 131:309-23. 2007
    ..Together, these findings point to a central role of RSUME in the regulation of sumoylation and, hence, several critical regulatory pathways in mammalian cells...
  100. ncbi Ribosomal protein S3: a KH domain subunit in NF-kappaB complexes that mediates selective gene regulation
    Fengyi Wan
    Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892, USA
    Cell 131:927-39. 2007
    ..Our observations provide insight into how NF-kappaB selectively controls gene expression...
  101. ncbi I kappa B alpha promoter polymorphisms in patients with systemic lupus erythematosus
    Chia Hui Lin
    Division of Rheumatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100 Zihyou 1st Road, Kaohsiung City 807, Taiwan
    J Clin Immunol 28:207-13. 2008
    To investigate the associations of IkappaBalpha gene polymorphisms with the development and clinical manifestations of systemic lupus erythematosus (SLE), 110 patients with SLE and 120 unrelated healthy controls were enrolled in this ..

Research Grants65

  1. CONTROL OF TNF SIGNALING BY NFKB
    ALBERT BALDWIN JR; Fiscal Year: 2003
    ..that TNFalpha and IFNgamma synergize at the level of NF-kappaB activation through the enhanced degradation of IkappaBalpha and the de novo degradation of IkappaBbeta which leads to a persistent activtion of NF-kappaB...
  2. Alcohol, iNOS upregulation, leaky gut & liver disease
    Ali Keshavarzian; Fiscal Year: 2009
    ..We predict i) E activates NF-kappaB by degrading IkappaBalpha;ii) preventing NF-kappaB activation prevents E-induced iNOS upregulation &its consequences...
  3. MEDIATORS AND MODIFIERS OF NF-kappaB IN INSULIN RESISTANCE
    Steven E Shoelson; Fiscal Year: 2010
    ..the expression of IKKi/epsilon, a Ser/Thr kinase that inhibits insulin signaling;and IkappaBzeta, unlike IkappaBalpha, selectively increases expression of a few interesting NF-kappaB targets such as IL-6...
  4. NF-kappaB Regulation by Androgen Receptor
    ALBERT BALDWIN JR; Fiscal Year: 2004
    ..indicate that androgens potently suppress NF-KB activation through a mechanism which involves inhibition of IkappaBalpha degradation...
  5. NEOADJUVANT THERAPY OF OR CANCER BY INHIBITING NF-KAPPAB
    Cun Yu Wang; Fiscal Year: 2003
    ..We will utilize adenovirus-mediated delivery of super-repressor-IkappaBalpha and proteasome inhibitors to block the activation of NF-kappaB in vivo and determine whether these approaches ..
  6. Mechanism of Constitutive NF-kappa B Activity
    Shigeki Miyamoto; Fiscal Year: 2007
    ..signals normally occurs only transiently since NF-kappaB activates synthesis of its own inhibitor, IkappaBalpha, which enters the nucleus, removes NF-kappaB from DNA binding sites, and exports it out to the cytoplasm to ..
  7. Negative regulation of NF-kB and inflammation by TAX1BP1
    Edward W Harhaj; Fiscal Year: 2012
    ..LPS) is normally transient due to the upregulation of multiple negative feedback inhibitors, including IkBa and A20 (also known as TNFAIP3)...
  8. Alex B Lentsch; Fiscal Year: 2014
    ..We have found a major defect in the processing of the cytoplasmic inhibitor of NF-kB, IkBa, in old mice...
  9. JAROSLAW WALDEMAR ZMIJEWSKI; Fiscal Year: 2015
    ..translocation of NF-[unreadable]B, by examining the effects of AMPK activation on IKK-dependent phosphorylation of IkBa, SCF-bTrCP mediated ubiquitination of phosphorylated IkBa and degradation of ubiquitinated IkBa by the 26S ..
  10. FUNCTIONAL ANALYSIS OF THE MOUSE-PELLE-LIKE KINASE
    Maureen Harrington; Fiscal Year: 2003
    ..of sequence similarity is shared between the mammalian NF- kappaB/c-rel family and its cytoplasmic inhibitor IkappaBalpha, and the Drosophila Dorsal protein and its regulator Cactus...
  11. Astrocytes Play a Critical Role in the Pathology of EAE
    JOHN ROLAND BETHEA; Fiscal Year: 2013
    ..autoimmune encephalomyelitis (EAE), taking advantage of a transgenic mouse model generated in our laboratory (GFAP-IkBa-dn mice) where NF-kB is functionally inactivated in cells expressing GFAP, such as astrocytes and non-myelinating ..
  12. Reactive oxygen species in Ni(II) carcinogenesis
    Xianglin Shi; Fiscal Year: 2012
    ..We will use overexpression of DN-NFAT, DN-IkappaBalpha and DN- IKKbeta to investigate the involvement of NFAT and NFkappaB in nickel-cell transformation and induced ..
  13. Jay A Nelson; Fiscal Year: 2016
    ..pathways including two potential antiviral cytokines IL-1 and TNF-[unreadable] as well as the NF?B inhibitor IkBa ...
  14. Immature intestinal NF-kB regulation, probiotics, and necrotizing enterocolitis
    Erika C Claud; Fiscal Year: 2013
    ..This proposal is designed to 1. Assess possible mechanisms behind deficient down-regulation of NF-kB signaling via IkBa and A20 in immature IEC. 2...
  15. Elucidating the Fas-activated inflammation-signaling complex (FISC)
    Mihail Iordanov; Fiscal Year: 2013
    ..of FISC, Fas ligation causes the activation of the TGFb-Activated Kinase-1 (TAK1) and the Inhibitor of NF-kB-a (IkBa)-phosphorylating Kinase-b (IKKb)...
  16. CLYDE JASON WRIGHT; Fiscal Year: 2014
    ..Interventions aimed at preventing the development of BPD will reduce the impact of this major public health burden. ..
  17. MOLECULAR MECHANISMS OF SEPTIC SHOCK
    JACK HAWIGER; Fiscal Year: 2003
    ..of NF- kappaB requires signal-dependent phosphorylation and intracellular proteolysis of inhibitory molecules, IkappaBalpha, and epsilon, sequestering NF-kappaB in cytoplasm...
  18. MECHANISM OF HTLV-I TAX-MEDIATED PHOSPHORYLATION OF IKBA
    EMMETT CUNNINGHAM; Fiscal Year: 2000
    ..that HTLV-I Tax-induced activation of NF-kappaB is preceded by the phosphorylation and degradation of IkappaBalpha, a cytoplasmic inhibitory protein that acts to sequester NF-kappaB in the host cytoplasm...
  19. Exploring How HTLV-1 Tax Induces T Cell Leukemia
    Warner Greene; Fiscal Year: 2006
    ..tumors by preparing and studying transgenic animals conditionally expressing Tax or a nondegradable mutant of IkappaBalpha that potently inhibits NF-kappaB/Rel activation by Tax (Specific Aim 1)...
  20. TNF-Induced Apoptosis of Lymphocytes in Aged Humans
    Sudhir Gupta; Fiscal Year: 2004
    ..the expression (by Western blotting) and activation of IKKb (by IKK immune complex kinase assay using GST- IkBa with cytoplasmic extracts of TNR-treated T cells) following treatment with TNF-a, [d] determine the phosphorylation ..
  21. Cancer Chemoprevention by Pomegranate Fruit Extract
    Farrukh Afaq; Fiscal Year: 2006
    ..normal human epidermal keratinocytes (NHEK) with PFE inhibits DVB-mediated degradation and phosphorylation of IkappaBalpha, activation of IKKalpha and NFkappaB...
  22. NMR Studies or I-kappa B alpha and its interaction with NF-kappa B
    Carla Cervantes; Fiscal Year: 2009
    ..Project Summary The regulation of the transcription factor Nuclear Factor Kappa B (NF-kB) by its inhibitor, IkBa, is critical for normal cell growth and misregulation is associated with many diseases...
  23. Activation of Skin Cells and Transcription Factors by S*
    Robert Swerlick; Fiscal Year: 2001
    ..nucleus; examine whether irritant treatment of HDMEC, HK, or HDF induces the phosphorylation and ubiquitination of IkBa, necessary steps for proteosome mediated degradation; examine whether translocated NF-kB complexes are capable of ..
  24. Mechanisms of Cardioprotection
    Roberto Bolli; Fiscal Year: 2007
    ..HSF1, STAT1, and STAT3) in HO-1 upregulation will be established by the use of a novel transdominant IkappaBalpha mutant mouse with cardiac-specific repression of NF-kappaB activity, knockouts for HIF-1alpha, HSF1, and three ..
  25. ALLERGIC AIRWAY RESPONSES--IMMUNE DEVIATION AND MEMORY
    Mark Boothby; Fiscal Year: 2002
    ..The other transgene [IkappaBalpha(deltaN)] inhibits signaling through the NF- kappaB/Rel pathway in T cells...
  26. Gene Specific Regulation of NFkB by Nuclear IkBa in Inflammation and Cancer
    Ivana Vancurova; Fiscal Year: 2010
    ....
  27. IKK-NF-kB pathways in viral-induced lung inflammation
    Roberto Garofalo; Fiscal Year: 2004
    ..cells occurs via the coordinated activation of the IkB-kinase (IKK) complex, proteolytic degradation of the IkBa inhibitor and nuclear translocation of the nuclear factor (NF) kappa-kB transactivating subunits RelA and p50...
  28. Oxidative stress and IkBalpha modification
    Brett Spear; Fiscal Year: 2002
    ..Recently, several groups have used in vitro systems to show that the SUMO can be conjugated to IkBa in a manner that is similar to polyubiquitination of this molecule...
  29. Structure-Function Relationship of Tumor Suppressors
    Junan Li; Fiscal Year: 2009
    ..funding period we obtained important findings suggesting that each of the four important proteins gankyrin, IkappaBalpha, Tax, and SEI-1 interacts with cyclin-dependent kinase 4 (CDK4), with potentially different mechanisms...
  30. NF-KAPPA BS IN VIVO ROLE IN DERMATITIS AND ANGIOGENESIS
    JOHN KLEMENT; Fiscal Year: 1999
    ..NF-kappaB's role in vivo, this grant proposes the following: 1) Study of the development of dermatitis in the IkappaBalpha deficient mice. In this animal model, the IkappaBalpha gene has been deleted via homologous recombination...
  31. MODULATION OF ENDOTHELIAL CELL RESPONSES BY A20
    Christiane Ferran; Fiscal Year: 2001
    ..e., E-selectin, IL-8 and IkBa. The inhibitory action of A20 is in part, or totally, due to blockade of NF-kB...
  32. Mentored Patient-Oriented Research Career Development Aw
    ASHER SCHACHTER; Fiscal Year: 2004
    ..suppress inflammatory and other nuclear factor kappa B (NF-kB)-dependent processes by inducing expression of IkB alpha (IkBa), which inhibits activation of NF-kB...
  33. REGULATION OF C-REL BY IKB-ALPH
    Mark Hannink; Fiscal Year: 2003
    ..We are using the c-Rel transcription factor and its inhibitor, IkappaBalpha, as a model system to understand how the directional transport of proteins between the nucleus and the ..
  34. Effects of Heat and/or Radiation on Proteasome Function
    William McBride; Fiscal Year: 2004
    ..For example, the rate of degradation of IkappaBalpha is slowed, with consequences for NF-kB activation and cell survival...
  35. Nuclear Translocation of I-kappaB-alpha as a Therapeutic Target
    Ivana Vancurova; Fiscal Year: 2007
    ..that as opposed to other cell types, resting human neutrophils contain predominant amount of NFkB inhibitor, IkBa, in the nucleus, and this increased nuclear accumulation of IkBa results in the inhibition of NFkB activity and ..
  36. PS-341 in Hepatocellular Carcinoma: A Phase II Trial
    Jordan Berlin; Fiscal Year: 2004
    ..By inhibiting proteasome 26S, PS 341 prevents the ubiquitination and degradation of IkappaBalpha, which remains bound to NF-?B, preventing activation of NF-?B...
  37. CD40 COSTIMULATION AND TRANSPLANTATION
    David Perkins; Fiscal Year: 2003
    ..the DO11 TCR transgene, which is cross-reactive with I-Ab, plus null alleles of either CD40, CD40L, c-Rel, or IkBa (DN), a dominant negative inhibitor of NF-kB...
  38. Mechanisms of Tumorigenesis in Pancreatic Epithelial Cells
    Paul Chiao; Fiscal Year: 2009
    ..tumorigenicity in orthotopic mouse model;(2) the K-ras downstream target genes were identified;(3) the mutant IkappaBalpha (S32, 36A) mediated inhibition of constitutive NF-kappaB activation suppressed liver metastasis of pancreas ..
  39. Molecular analysis of thymic negative selection
    Linda Clayton; Fiscal Year: 2007
    ..of IkappaBNS protein expression in the thymus have been determined and are very different flora those of IkappaBalpha. In addition, IkappaBNS localizes to the nucleus...
  40. PROTEASOME INHIBITORS FOR THE TREATMENT OF STROKE
    Peter Elliott; Fiscal Year: 1999
    ..Activation of NF-kB results from proteolysis of its inhibitory protein, IkBa, via the intracellular ubiquitin-proteasome pathway...
  41. Autoimmunity in IEX-1- transgenic mice
    Mei Wu; Fiscal Year: 2006
    ..vivo and in vitro effects of IEX-1 on the life span of Ag-stimulated T cells with or without expressing a truncated IkBa (N) by crossbreeding T cell receptor/IEX-l-Tg mice with IkBa (N)- mice...
  42. HIV AND NF-KB INTERACTIONS IN MONOCYTES
    Carlos Paya; Fiscal Year: 2001
    ..from this lab have identified components of NF-kB that are unique to macrophages, this includes the targeting of IkBa and nuclear translocation of NF-kB following HIV infection...
  43. Peptide Regulators of Angiogenesis
    Michael Simons; Fiscal Year: 2005
    ..degradation of a small number of proteins including hypoxia-inducible factor (HIF)- 1I A and NFKB inhibitor IKBA. In addition, PR39 induces expression of FGF signaling proteins FGF receptor I and syndecan-4...
  44. MECHANISMS OF SIGNAL INDUCED UBIQUITINATION OF IKBA
    Zhijian Chen; Fiscal Year: 2002
    ..abstract_text> ..
  45. REGULATION LYMPHOCYTE PROLIFERATION AND DIFFERENTIATIO
    JOAN PRESS; Fiscal Year: 2004
    ..AICD, and maintaining cell viability during the effector phase; 3) to characterize tissue-specific modifications of IkBa and the basis for differential association with Rel family members...
  46. ROLE OF NF-KB IN THE SUPPRESSION OF IMMUNITY BY ETHANOL
    Raphael Rubin; Fiscal Year: 2003
    ..Ethanol inhibits the signal induced phosphorylation of the NFkB inhibitor IkappaBalpha, thereby blocking the translocation of NFkB to the nucleus and the activation NFkB response genes...
  47. Regulation and Function of MEKK3 in Dendritic Cells
    Bing Su; Fiscal Year: 2009
    ..The mitogen-activated protein kinase (MAPK) and the IkappaBalpha kinase (IKK) are the main targets of the TLR pathways in DCs and other cells in immune system...
  48. MINORITY PREDOCTORAL FELLOWSHIP PROGRAM
    Gabriel Pineda; Fiscal Year: 2006
    Signal induced phosphorylation of IkappaBalpha, the inhibitor of NF-kappaB leads to its subsequent poly-ubiquitination and degradation by the ubiquitin proteasome pathway...
  49. MOLECULAR MECHANISMS OF DELAYED PRECONDITIONING
    RAKESH KUKREJA; Fiscal Year: 2006
    ..directed against the p65 subunit of NFKB, proteasome or nuclear localization inhibitors, overexpression of IkBa mutant with adenoviral constructs and p50 gene knockout mice we will determine the cause and effect of p50 and p65 ..
  50. Role of NF-kB Activity in Muyltiple Myeloma
    Stephanie Markovina; Fiscal Year: 2009
    ..The specific goals of this proposal are to delineate the cis-elements of IkBa that are required for it to be a substrate of bortezomib-resistant degradation, and to identify novel upstream ..
  51. TNF Modulation of Mammary Proliferation
    MARGOT IP; Fiscal Year: 2007
    ..In Aim 1, the mechanism by which NFkBI/p50 expression and activity are regulated by TNF in normal and malignant MEC will be investigated...
  52. REGULATION OF CYTOKINE GENES IN MUCOSAL VIRAL INFECTION
    Allan Brasier; Fiscal Year: 2006
    ..Expression of dominant-negative NF-KB and CBP/p300 coactivators will be used to determine their effect on coactivator recruitment. These studies will identify signaling mechanisms and protein interactions in viral-induced inflammation. ..
  53. Mechanisms for Hormone-Dependent NF-kB Activation
    Allan Brasier; Fiscal Year: 2007
    ..These studies will identify new therapeutic targets that can disrupt the vicious cycle of inflammation and atherosclerosis. ..
  54. Neuroimmune Communication at the Blood Brain Barrier
    Ning Quan; Fiscal Year: 2009
    ..I IL-1 receptor, IL-1r1) is mostly expressed on CNS endothelial cells, 2) IL-1-responsive immediate early gene IkappaBalpha is induced primarily in CNS endothelium after central IL-1 injection;3) inflammatory mediators such as the ..
  55. Pathophysiology of Neuroimmune Communication
    Ning Quan; Fiscal Year: 2003
    ..The results will also provide critical information regarding the use of anti-inflammatory drugs for the treatment of CNS diseases. ..
  56. Heat shock proteins and alcohol induced liver injury
    Pranoti Mandrekar; Fiscal Year: 2006
    ....
  57. Cell type gene delivery and alcoholic liver disease
    Michael Wheeler; Fiscal Year: 2006
    ..In addition, through didactic training, and interactions with his mentor and key faculty, the applicant will acquire new skills that will allow him to become a successful member of the alcohol research community. ..
  58. Protective Mechanism of an Anti-Inflammatory Herbal Mix
    Ali Banan; Fiscal Year: 2006
    ..abstract_text> ..
  59. EGF, Oxidants & Intestinal Barrier Integrity
    Ali Banan; Fiscal Year: 2006
    ..abstract_text> ..
  60. MOLECULAR TARGETS OF NITRIC OXIDE IN CARDIAC TRANSPLANTS
    GALEN PIEPER; Fiscal Year: 2004
    ..These studies will provide a novel mechanism to explain the pathogenesis of dyskinesis and graft failure during cardiac transplant rejection. ..
  61. iNOS Posttranslational Regulation in Cardiac Rejection
    GALEN PIEPER; Fiscal Year: 2009
    ..A better understanding of this molecular process may lead to better strategies to prevent injury cardiac cells in these patients. ..
  62. Role of ghrelin in intestinal inflammation
    Dezheng Zhao; Fiscal Year: 2008
    ....
  63. Tissue engineering of small diameter vascular graft
    Changyi Chen; Fiscal Year: 2006
    ..Success of this proposal will directly indicate the clinical applications of tissue engineered small diameter vascular grafts. ..
  64. Neurobiology of high alcohol-seeking behavior
    WILLIAM JOSEPH MCBRIDE; Fiscal Year: 2010
    ....
  65. NF-KB SIGNAL TRANSDUCTION IN BRAIN INJURY
    KEITH PENNYPACKER; Fiscal Year: 2003
    ..These studies will define the role of NF-kB in the process of brain injury and subsequent repair and regeneration processes. ..