IKK alpha

Summary

Gene Symbol: IKK alpha
Description: conserved helix-loop-helix ubiquitous kinase
Alias: IKBKA, IKK-alpha, IKK1, IKKA, NFKBIKA, TCF16, inhibitor of nuclear factor kappa-B kinase subunit alpha, I-kappa-B kinase 1, I-kappa-B kinase-alpha, IKK-a kinase, IkB kinase alpha subunit, Nuclear factor NFkappaB inhibitor kinase alpha, TCF-16, transcription factor 16
Species: human

Top Publications

  1. 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
  2. ncbi Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex
    Zhanguo Gao
    Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA
    J Biol Chem 277:48115-21. 2002
  3. ncbi Formation of an IKKalpha-dependent transcription complex is required for estrogen receptor-mediated gene activation
    Kyu Jin Park
    Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA
    Mol Cell 18:71-82. 2005
  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. 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
  6. pmc Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase
    Mark Windheim
    MRC Protein Phosphorylation Unit, College of Life Sciences, The Sir James Black Centre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    Mol Cell Biol 28:1783-91. 2008
  7. ncbi Human T-cell lymphotropic virus type 1 tax induction of biologically Active NF-kappaB requires IkappaB kinase-1-mediated phosphorylation of RelA/p65
    ALISON M O'MAHONY
    Gladstone Institute for Virology and Immunology, Department of Medicine, University of California, San Francisco, California 94141, USA
    J Biol Chem 279:18137-45. 2004
  8. ncbi Identification and characterization of the IKKalpha promoter: positive and negative regulation by ETS-1 and p53, respectively
    Lubing Gu
    Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 279:52141-9. 2004
  9. doi Tumor necrosis factor receptor-associated factor-1 enhances proinflammatory TNF receptor-2 signaling and modifies TNFR1-TNFR2 cooperation
    A Wicovsky
    Department of Internal Medicine II, Division of Molecular Internal Medicine, University Hospital Wurzburg, Wurzburg, Germany
    Oncogene 28:1769-81. 2009
  10. 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

Research Grants

  1. Role of IKK in NSCLC: Modulation of SMRT and NF-kappaB
    Marty W Mayo; Fiscal Year: 2012
  2. Negative regulation of NF-kB and inflammation by TAX1BP1
    Edward W Harhaj; Fiscal Year: 2012
  3. ALBERT SIDNEY BALDWIN; Fiscal Year: 2014
  4. David C Parker; Fiscal Year: 2015
  5. The Role of IKK and NF-kappaB in Controlling mTOR Signaling and TSC Progression
    Hancai Dan; Fiscal Year: 2012
  6. ALBERT SIDNEY BALDWIN; Fiscal Year: 2014
  7. Structural and functional studies of the IkappaB kinase (IKK) complex
    Hao Wu; Fiscal Year: 2013
  8. IKKa-Dependent Negative Feedback Control of Non-Canonical NF-kB Activation
    Genhong Cheng; Fiscal Year: 2012
  9. Mechanisms for Hormone-Dependent NF-kB Activation
    Allan Brasier; Fiscal Year: 2007
  10. Sanjay Gupta; Fiscal Year: 2014

Detail Information

Publications233 found, 100 shown here

  1. 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
    ..Stimulation of RASF with leptin activated IkappaB kinase alpha/beta (IKK alpha/beta), p65 phosphorylation at Ser(276), p65 translocation from the cytosol to the nucleus, and kappaB-luciferase ..
  2. ncbi Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex
    Zhanguo Gao
    Pennington Biomedical Research Center, Louisiana State University, Baton Rouge 70808, USA
    J Biol Chem 277:48115-21. 2002
    ....
  3. ncbi Formation of an IKKalpha-dependent transcription complex is required for estrogen receptor-mediated gene activation
    Kyu Jin Park
    Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA
    Mol Cell 18:71-82. 2005
    ..These results suggest that IKKalpha plays a major role in regulating the biological effects of estrogen via its promoter association and modification of components of the transcription complex...
  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. 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...
  6. pmc Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase
    Mark Windheim
    MRC Protein Phosphorylation Unit, College of Life Sciences, The Sir James Black Centre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    Mol Cell Biol 28:1783-91. 2008
    ..Our data suggest a model in which the recruitment of the NEMO-IKK complex to K63-pUb-IRAK1 and the recruitment of the TAK1 complex to TRAF6 facilitate the TAK1-catalyzed activation of IKK by the TRAF6-IRAK1 complex...
  7. ncbi Human T-cell lymphotropic virus type 1 tax induction of biologically Active NF-kappaB requires IkappaB kinase-1-mediated phosphorylation of RelA/p65
    ALISON M O'MAHONY
    Gladstone Institute for Virology and Immunology, Department of Medicine, University of California, San Francisco, California 94141, USA
    J Biol Chem 279:18137-45. 2004
    ..studies of the human T-cell lymphotropic virus type 1 (HTLV-1) Tax oncoprotein, we have uncovered a new function of IKK1 required for complete activation of the NF-kappaB transcriptional program...
  8. ncbi Identification and characterization of the IKKalpha promoter: positive and negative regulation by ETS-1 and p53, respectively
    Lubing Gu
    Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Biol Chem 279:52141-9. 2004
    ..Furthermore, loss of p53-mediated control over ETS-1-dependent transactivation of IKKalpha may represent a novel pathway for the constitutive activation of NF-kB-mediated gene expression and therapy resistance in cancer...
  9. doi Tumor necrosis factor receptor-associated factor-1 enhances proinflammatory TNF receptor-2 signaling and modifies TNFR1-TNFR2 cooperation
    A Wicovsky
    Department of Internal Medicine II, Division of Molecular Internal Medicine, University Hospital Wurzburg, Wurzburg, Germany
    Oncogene 28:1769-81. 2009
    ..Thus, TRAF1 shifts the quality of integrated TNFR1-TNFR2 signaling from apoptosis induction to proinflammatory NFkappaB signaling...
  10. 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...
  11. pmc A herpesvirus virulence factor inhibits dendritic cell maturation through protein phosphatase 1 and Ikappa B kinase
    Huali Jin
    Department of Microbiology and Immunology M C 790, College of Medicine, University of Illinois, Chicago, 835 South Wolcott Avenue, Chicago, IL 60612, USA
    J Virol 85:3397-407. 2011
    ..Deletions or mutations in either domain abolish the activity of γ(1)34.5. These results suggest that the control of IκB kinase dephosphorylation by γ(1)34.5 represents a critical viral mechanism to disrupt dendritic cell functions...
  12. pmc Defective nuclear IKKα function in patients with ectodermal dysplasia with immune deficiency
    Stephane T Temmerman
    Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland 20892, USA
    J Clin Invest 122:315-26. 2012
    ..Our findings suggest that NEMO regulates the nuclear function of IKKα and offer new insights into the mechanisms underlying diminished NF-κB signaling in patients with EDI...
  13. ncbi Decoy receptor 3 expression in AsPC-1 human pancreatic adenocarcinoma cells via the phosphatidylinositol 3-kinase-, Akt-, and NF-kappa B-dependent pathway
    Pei Hsuan Chen
    School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan
    J Immunol 181:8441-9. 2008
    ....
  14. ncbi High concentration of antioxidants N-acetylcysteine and mitoquinone-Q induces intercellular adhesion molecule 1 and oxidative stress by increasing intracellular glutathione
    Tapan K Mukherjee
    Department of Internal Medicine, Pulmonary Division, University of Utah Health Science Center, Salt Lake City, UT 84112, USA
    J Immunol 178:1835-44. 2007
    ....
  15. pmc Notch-1 activates estrogen receptor-alpha-dependent transcription via IKKalpha in breast cancer cells
    L Hao
    Breast Cancer Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL, USA
    Oncogene 29:201-13. 2010
    ..Our observations suggest that a hitherto unknown Notch-1/ERalpha chromatin crosstalk mediates Notch signaling effects in ERalpha-positive breast cancer cells and contributes to regulate the transcriptional functions of ERalpha itself...
  16. pmc IkappaB kinase (IKK)-associated protein 1, a common component of the heterogeneous IKK complex
    F Mercurio
    Signal Pharmaceuticals, Inc, San Diego, California 92121, USA
    Mol Cell Biol 19:1526-38. 1999
    ..a large multiprotein complex, the IkappaB kinase (IKK) signalsome, which contains two regulated IkappaB kinases, IKK1 and IKK2, that can each phosphorylate IkappaBalpha and IkappaBbeta...
  17. pmc Modulation of the nuclear factor kappa B pathway by Shp-2 tyrosine phosphatase in mediating the induction of interleukin (IL)-6 by IL-1 or tumor necrosis factor
    M You
    Burnham Institute, La Jolla, California 92037, USA
    J Exp Med 193:101-10. 2001
    ..These results elucidate a novel mechanism of Shp-2 in cytokine signaling by specifically modulating the NF-kappa B pathway in a MAP kinase-independent fashion...
  18. 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
    ..Collectively, the data suggest that hTid-1 represses the activity of NF-kappaB through physical and functional interactions with the IKK complex and IkappaB and, in doing so, it modulates cell growth and death...
  19. 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...
  20. 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...
  21. 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...
  22. pmc Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase
    S Nemoto
    Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    Mol Cell Biol 18:7336-43. 1998
    ..The formation of the MEKK1-IKK complex versus the NIK-IKK complex may provide a molecular basis for regulation of the IKK complex by various extracellular signals...
  23. ncbi Functional interactions of transforming growth factor beta-activated kinase 1 with IkappaB kinases to stimulate NF-kappaB activation
    H Sakurai
    Discovery Research Laboratory, Tanabe Seiyaku Co, Ltd, 16 89 Kashima 3 chome, Yodogawa ku, Osaka 532 8505, Japan
    J Biol Chem 274:10641-8. 1999
    ..These results demonstrated a novel signaling pathway to NF-kappaB activation through TAK1 in which TAK1 may act as a regulatory kinase of IKKs...
  24. pmc The alpha and beta subunits of IkappaB kinase (IKK) mediate TRAF2-dependent IKK recruitment to tumor necrosis factor (TNF) receptor 1 in response to TNF
    A Devin
    Department of Cell and Cancer Biology, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Mol Cell Biol 21:3986-94. 2001
    ....
  25. ncbi Tumor necrosis factor receptor-associated factor 1 gene overexpression in B-cell chronic lymphocytic leukemia: analysis of NF-kappa B/Rel-regulated inhibitors of apoptosis
    Gerd Munzert
    Abteilung Innere Medizin III and Abteilung Innere Medizin I, Universitat Ulm, Ulm, Germany
    Blood 100:3749-56. 2002
    ..Thus, although our study revealed a common expression pattern of NF-kappaB/Rel-regulated inhibitors of apoptosis, our findings indicate an IKK-independent regulation of TRAF1 in B-CLL...
  26. ncbi PAN1/NALP2/PYPAF2, an inducible inflammatory mediator that regulates NF-kappaB and caspase-1 activation in macrophages
    Jean Marie Bruey
    Burnham Institute, La Jolla, California 92037, USA
    J Biol Chem 279:51897-907. 2004
    ..We propose that PAN1 functions as a modulator of the activation of NF-kappaB and pro-caspase-1 in macrophages...
  27. ncbi Constitutive and interleukin-1-inducible phosphorylation of p65 NF-{kappa}B at serine 536 is mediated by multiple protein kinases including I{kappa}B kinase (IKK)-{alpha}, IKK{beta}, IKK{epsilon}, TRAF family member-associated (TANK)-binding kinase 1 (TBK
    Holger Buss
    Institute of Pharmacology, Medical School Hannover, Carl Neuberg Strasse 1, D 30625 Hannover, Germany
    J Biol Chem 279:55633-43. 2004
    ....
  28. pmc Cytotoxic necrotizing factor 1 prevents apoptosis via the Akt/IkappaB kinase pathway: role of nuclear factor-kappaB and Bcl-2
    Alessandro Giamboi Miraglia
    Departments of Drug Research and Evaluation and Technology, Istituto Superiore di Sanita, Rome, Italy
    Mol Biol Cell 18:2735-44. 2007
    ..It is worth noting that the ability of a bacterial toxin to induce such a remodeling of the mitochondrial network is herein reported for the first time. The possible pathophysiological relevance of this finding is discussed...
  29. 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...
  30. ncbi IKK-1 and IKK-2: cytokine-activated IkappaB kinases essential for NF-kappaB activation
    F Mercurio
    Signal Pharmaceuticals, Inc, 5555 Oberlin Drive, San Diego, CA 92121, USA
    Science 278:860-6. 1997
    ..Mutant versions of IKK-2 had pronounced effects on RelA nuclear translocation and NF-kappaB-dependent reporter activity, consistent with a critical role for the IKK kinases in the NF-kappaB signaling pathway...
  31. ncbi IKK-gamma is an essential regulatory subunit of the IkappaB kinase complex
    D M Rothwarf
    Department of Pharmacology, University of California San Diego, La Jolla 92093 0636, USA
    Nature 395:297-300. 1998
    ..IKK-gamma interacts preferentially with IKK-beta and is required for the activation of the IKK complex. An IKK-gamma carboxy-terminal truncation mutant that still binds IKK-beta blocks the activation of IKK and NF-kappaB...
  32. ncbi Positive and negative regulation of IkappaB kinase activity through IKKbeta subunit phosphorylation
    M Delhase
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0636, USA
    Science 284:309-13. 1999
    ..Once activated, IKKbeta autophosphorylated at a carboxyl-terminal serine cluster. Such phosphorylation decreased IKK activity and may prevent prolonged activation of the inflammatory response...
  33. ncbi The human herpes virus 8-encoded viral FLICE inhibitory protein physically associates with and persistently activates the Ikappa B kinase complex
    Li Liu
    Hamon Center for Therapeutic Oncology Research and Division of Hematology Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8593, USA
    J Biol Chem 277:13745-51. 2002
    ..Our results suggest that HHV8 vFLIP might contribute to the persistent NF-kappaB activation observed in PEL cells by associating with and stimulating the activity of the cellular IKK complex...
  34. pmc Tetrameric oligomerization of IkappaB kinase gamma (IKKgamma) is obligatory for IKK complex activity and NF-kappaB activation
    Sebastian Tegethoff
    Cell Growth and Differentiation Program, Max Delbruck Center for Molecular Medicine, Robert Rossle Strasse 10, 13092 Berlin, Germany
    Mol Cell Biol 23:2029-41. 2003
    ..These data thus suggest that IKKgamma tetramerization enforces a spatial positioning of two kinase dimers to facilitate transautophosphorylation and activation...
  35. ncbi Induction of p100 processing by NF-kappaB-inducing kinase involves docking IkappaB kinase alpha (IKKalpha) to p100 and IKKalpha-mediated phosphorylation
    Gutian Xiao
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Biol Chem 279:30099-105. 2004
    ..These data also provide the first evidence for explaining why overexpression of IKKalpha or its activation by many other stimuli such as tumor necrosis factor and mitogens fails to induce p100 processing...
  36. ncbi SMRT derepression by the IkappaB kinase alpha: a prerequisite to NF-kappaB transcription and survival
    Jamie E Hoberg
    Department of Biochemistry and Molecular Genetics, The University of Virginia, Charlottesville, VA 22908, USA
    Mol Cell 16:245-55. 2004
    ..Our work provides evidence that IKKalpha orchestrates SMRT derepression, a prerequisite for NF-kappaB transcription and survival...
  37. ncbi Interleukin-1beta induction of NFkappaB is partially regulated by H2O2-mediated activation of NFkappaB-inducing kinase
    Qiang Li
    Department of Anatomy and Cell Biology, College of Medicine, The University of Iowa, Iowa City, Iowa 52242, USA
    J Biol Chem 281:1495-505. 2006
    ..In summary, our studies have demonstrated that redox regulation of NIK by H2O2 is mechanistically important in IL-1beta induction of NFkappaB activation...
  38. ncbi IKK alpha regulates estrogen-induced cell cycle progression by modulating E2F1 expression
    Zheng Tu
    Lilly Research Laboratories, Indianapolis, Indiana 46285, USA
    J Biol Chem 281:6699-706. 2006
    ..Taken together, these data suggest a novel mechanism by which IKKalpha can influence estrogen-mediated cell cycle progression through its regulation of E2F1...
  39. ncbi Regulation and function of IKK and IKK-related kinases
    Hans Hacker
    Department of Infectious Diseases, St Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA
    Sci STKE 2006:re13. 2006
    ..Together, the IKKs and IKK-related kinases are instrumental for activation of the host defense system. This Review focuses on the functions of IKK and IKK-related kinases and the molecular mechanisms that regulate their activities...
  40. ncbi Promoter-dependent effect of IKKalpha on NF-kappaB/p65 DNA binding
    Geoffrey Gloire
    GIGA Research, Virology Immunology, and Medical Chemistry Units, University of Liege, B 4000 Liege, Belgium
    J Biol Chem 282:21308-18. 2007
    ..We conclude that nuclear IKKalpha is required for p65 DNA binding in a gene-specific manner...
  41. ncbi IKKalpha enhances human keratinocyte differentiation and determines the histological variant of epidermal squamous cell carcinomas
    Rodolfo Moreno-Maldonado
    Department of Epithelial Biology, CIEMAT, Madrid, Spain
    Cell Cycle 7:2021-9. 2008
    ..The tight correlation between the properties of both murine and human ASCC variants strongly suggests that IKKalpha is responsible for the development of this human SCC variant...
  42. doi Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction
    Tobias L Haas
    Division of Apoptosis Regulation, German Cancer Research Center DKFZ, 69120 Heidelberg, Germany
    Mol Cell 36:831-44. 2009
    ..Finally, we demonstrate that sustained stability of the TNF-RSC requires LUBAC's enzymatic activity, thereby adding a third form of ubiquitin linkage to the triggering of TNF signaling by the TNF-RSC...
  43. pmc Allosteric regulation of the ubiquitin:NIK and ubiquitin:TRAF3 E3 ligases by the lymphotoxin-beta receptor
    Hideki Sanjo
    Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA
    J Biol Chem 285:17148-55. 2010
    ..These results indicate the LTbetaR modifies the ubiquitin:NIK E3 ligase, and also acts as an allosteric regulator of the ubiquitin:TRAF E3 ligase...
  44. pmc NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176
    L Ling
    Tularik, Inc, Two Corporate Drive, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 95:3792-7. 1998
    ..Conversely, a mutant form of IKK-alpha containing glutamic acid at residue 176 is constitutively active. Thus, the phosphorylation of IKK-alpha on Ser-176 by NIK may be required for cytokine-mediated NF-kappaB activation...
  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. 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...
  47. ncbi NF-kappaB is a target of AKT in anti-apoptotic PDGF signalling
    J A Romashkova
    Thurston Arthritis Research Center, University of North Carolina at Chapel Hill, 27599 7280, USA
    Nature 401:86-90. 1999
    ..These findings establish a role for NF-kappaB in growth factor signalling and define an anti-apoptotic Ras/PI(3)K/Akt/IKK/NF-kappaB pathway, thus linking anti-apoptotic signalling with transcription machinery...
  48. pmc IkappaB kinase alpha (IKKalpha) regulation of IKKbeta kinase activity
    Y Yamamoto
    Division of Hematology Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75235 8594, USA
    Mol Cell Biol 20:3655-66. 2000
    ..These results indicate that IKKalpha, in addition to its previously described ability to phosphorylate IkappaBalpha, can increase the ability of IKKbeta to phosphorylate IkappaBalpha...
  49. ncbi Regulation of beta-catenin function by the IkappaB kinases
    C Lamberti
    Division of Hematology Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 276:42276-86. 2001
    ....
  50. pmc Regulation of SRC-3 (pCIP/ACTR/AIB-1/RAC-3/TRAM-1) Coactivator activity by I kappa B kinase
    Ray Chang Wu
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    Mol Cell Biol 22:3549-61. 2002
    ..Taken together, our results not only reveal the IKK-mediated phosphorylation of SRC-3 to be a regulated event that plays an important role but also substantiate the role of SRC-3 in multiple signaling pathways...
  51. ncbi A novel PAAD-containing protein that modulates NF-kappa B induction by cytokines tumor necrosis factor-alpha and interleukin-1beta
    Loredana Fiorentino
    Burnham Institute, La Jolla, California 92037, USA
    J Biol Chem 277:35333-40. 2002
    ..These observations suggest a role for PAN2 in modulating NF-kappaB activity in cells, thus providing the insights into the potential functions of PAAD family proteins and their roles in controlling inflammatory responses...
  52. ncbi A resorcylic acid lactone, 5Z-7-oxozeaenol, prevents inflammation by inhibiting the catalytic activity of TAK1 MAPK kinase kinase
    Jun Ninomiya-Tsuji
    Department of Molecular Biology, Graduate School of Science, Nagoya University, and CREST, Japan Science and Technology Corporation, Chikusa ku, Nagoya 464 8602, Japan
    J Biol Chem 278:18485-90. 2003
    ..Furthermore, in vivo 5Z-7-oxozeaenol was able to inhibit picryl chloride-induced ear swelling. Thus, 5Z-7-oxozeaenol blocks proinflammatory signaling by selectively inhibiting TAK1 MAPKKK...
  53. ncbi Bcl10 activates the NF-kappaB pathway through ubiquitination of NEMO
    Honglin Zhou
    Department of Molecular Oncology, Genentech Inc 1 DNA Way, South San Francisco, California 94080, USA
    Nature 427:167-71. 2004
    ..Thus, the adaptor protein Bcl10 promotes activation of NF-kappaB transcription factors through paracaspase- and UBC13-dependent ubiquitination of NEMO...
  54. ncbi Activation of transcription factor NF-kappaB requires ELKS, an IkappaB kinase regulatory subunit
    Jeanette L Ducut Sigala
    Salk Institute for Biological Sciences, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Science 304:1963-7. 2004
    ..These cells were also not protected from apoptosis in response to cytokines. ELKS likely functions by recruiting IkappaBalpha to the IKK complex and thus serves a regulatory function for IKK activation...
  55. ncbi The C-terminal activating region 2 of the Epstein-Barr virus-encoded latent membrane protein 1 activates NF-kappaB through TRAF6 and TAK1
    Liming Wu
    Department of Biochemistry, Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong, China
    J Biol Chem 281:2162-9. 2006
    ..Thus, LMP1 utilizes two distinct pathways to activate NF-kappaB: a major one through CTAR2/TRAF6/TAK1/IKKbeta (canonical pathway) and a minor one through CTAR1/TRAF3/NIK/IKKalpha (noncanonical pathway)...
  56. pmc IkappaB kinase alpha-mediated derepression of SMRT potentiates acetylation of RelA/p65 by p300
    Jamie E Hoberg
    Department of Biochemistry and Molecular Genetics, Box 800733, University of Virginia, Charlottesville, Virginia 22908, USA
    Mol Cell Biol 26:457-71. 2006
    ....
  57. ncbi Molecular linkage between the kinase ATM and NF-kappaB signaling in response to genotoxic stimuli
    Zhao Hui Wu
    Department of Pharmacology, University of Wisconsin Madison, 301 SMI, 1300 University Avenue, Madison, WI 53706, USA
    Science 311:1141-6. 2006
    ..Thus, regulated nuclear shuttling of NEMO links two signaling kinases, ATM and IKK, to activate NF-kappaB by genotoxic signals...
  58. pmc In vitro treatment of human monocytes/macrophages with myristoylated recombinant Nef of human immunodeficiency virus type 1 leads to the activation of mitogen-activated protein kinases, IkappaB kinases, and interferon regulatory factor 3 and to the releas
    Giorgio Mangino
    Department of Biology University Roma Tre, Viale G Marconi 446, 00146 Rome, Italy
    J Virol 81:2777-91. 2007
    ..In addition, we have observed the activation of interferon regulatory factor 3, leading to the synthesis of beta interferon mRNA and protein, which in turn induces STAT2 phosphorylation. All of these effects require Nef myristoylation...
  59. ncbi Mitogen-activated protein kinases, inhibitory-kappaB kinase, and insulin signaling in human omental versus subcutaneous adipose tissue in obesity
    Nava Bashan
    Department of Clinical Biochemistry, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva 84103, Israel
    Endocrinology 148:2955-62. 2007
    ..Increased expression of stress-activated kinases and IKK and their phosphorylated forms in omental fat occurs in obesity, potentially contributing to differential roles of omental and sc fat in the pathophysiology of obesity...
  60. ncbi Proinflammatory stimuli induce IKKalpha-mediated phosphorylation of PIAS1 to restrict inflammation and immunity
    Bin Liu
    Division of Hematology Oncology, Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA
    Cell 129:903-14. 2007
    ..Our results identify a signaling pathway in which proinflammatory stimuli activate the IKKalpha-mediated sumoylation-dependent phosphorylation of PIAS1 for the immediate repression of inflammatory gene activation...
  61. ncbi IKKalpha shields 14-3-3sigma, a G(2)/M cell cycle checkpoint gene, from hypermethylation, preventing its silencing
    Feng Zhu
    Science Park Research Division, The University of Texas MD Anderson Cancer Center, Smithville, TX 78957, USA
    Mol Cell 27:214-27. 2007
    ..IKKalpha mutants that failed to bind to H3 did not restore the expression of 14-3-3sigma. Thus, IKKalpha protects the 14-3-3sigma locus from hypermethylation, which serves as a mechanism of maintaining genomic stability in keratinocytes...
  62. ncbi The deubiquitinating enzyme USP11 controls an IkappaB kinase alpha (IKKalpha)-p53 signaling pathway in response to tumor necrosis factor alpha (TNFalpha)
    Tomoko Yamaguchi
    Department of Molecular Genetics, Medical Research Institute, Tokyo Medical and Dental University, Yushima 1 5 45, Bunkyo ku, Tokyo, Japan
    J Biol Chem 282:33943-8. 2007
    ..Importantly, the ectopic expression of IKKalpha into cells silenced for USP11 restores p53 expression, demonstrating that USP11 functions as an upstream regulator of an IKKalpha-p53 signaling pathway...
  63. pmc Differential requirements for IKKalpha and IKKbeta in the differentiation of primary human osteoarthritic chondrocytes
    Eleonora Olivotto
    Istituti Ortopedici Rizzoli, Bologna, Italy
    Arthritis Rheum 58:227-39. 2008
    ..This study was undertaken to investigate the differential roles of each IKK in chondrocyte differentiation and hypertrophy...
  64. pmc Inhibition of IkappaB kinase by vaccinia virus virulence factor B14
    Ron A J Chen
    Department of Virology, Faculty of Medicine, Imperial College London, London, United Kingdom
    PLoS Pathog 4:e22. 2008
    ..This suggested that phosphorylation of these serine residues in the activation loop of IKKbeta is targeted by B14, and this was confirmed using Ab specific for phospho-IKKbeta...
  65. pmc IKKalpha is a critical coregulator of a Smad4-independent TGFbeta-Smad2/3 signaling pathway that controls keratinocyte differentiation
    Pascal Descargues
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Proc Natl Acad Sci U S A 105:2487-92. 2008
    ..We suggest that a TGFbeta-Smad2/3-IKKalpha axis is a critical Smad4-independent regulator of keratinocyte proliferation and differentiation...
  66. pmc Dynein light chain LC8 negatively regulates NF-kappaB through the redox-dependent interaction with IkappaBalpha
    Yuyeon Jung
    Department of Life Science, Division of Life and Pharmaceutical Sciences, and Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, 11 1 Daehyun Dong, Seodaemun gu, Seoul, Korea
    J Biol Chem 283:23863-71. 2008
    ..Together, our results indicate that LC8 binds IkappaBalpha in a redox-dependent manner and thereby prevents its phosphorylation by IKK. TRP14 contributes to this inhibitory activity by maintaining LC8 in a reduced state...
  67. pmc The IkappaB kinase complex: master regulator of NF-kappaB signaling
    Laura A Solt
    Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, 3800 Spruce Street OVH 200E, Philadelphia, PA, 19104 6045, USA
    Immunol Res 42:3-18. 2008
    ....
  68. pmc Compensatory IKKalpha activation of classical NF-kappaB signaling during IKKbeta inhibition identified by an RNA interference sensitization screen
    Lloyd T Lam
    Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 105:20798-803. 2008
    ..These results suggest that therapy for ABC DLBCL may be improved by targeting both IKKalpha and IKKbeta, possibly through CARD11 inhibition...
  69. pmc IKKalpha and IKKbeta regulation of DNA damage-induced cleavage of huntingtin
    Ali Khoshnan
    Biology Division 216 76, California Institute of Technology, Pasadena, California, USA
    PLoS ONE 4:e5768. 2009
    ..One stimulus may be the DNA damage that accumulates in neurons over time, and the subsequent activation of signaling pathways such as those regulated by IkappaB kinase (IKK), which can influence neurodegeneration in HD...
  70. doi High expression levels of IKKalpha and IKKbeta are necessary for the malignant properties of liver cancer
    Runqiu Jiang
    Liver Transplantation Center of the First Affiliated Hospital and Cancer Center, Nanjing Medical University, Nanjing, Jiangsu Province, People s Republic of China
    Int J Cancer 126:1263-74. 2010
    ..We anticipate that IKK-targeted gene therapy can be used in the treatment of HCC, a cancer that is notoriously resistant to radiation and chemotherapy...
  71. pmc Negative feedback in noncanonical NF-kappaB signaling modulates NIK stability through IKKalpha-mediated phosphorylation
    Bahram Razani
    Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, 609 Charles E Young Drive East, Los Angeles, CA 90095, USA
    Sci Signal 3:ra41. 2010
    ....
  72. pmc MicroRNAs modulate the noncanonical transcription factor NF-kappaB pathway by regulating expression of the kinase IKKalpha during macrophage differentiation
    Tao Li
    Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Nat Immunol 11:799-805. 2010
    ..Thus, a decrease in certain microRNAs probably prevents macrophage hyperactivation yet primes the macrophage for certain responses to proinflammatory stimuli...
  73. doi IKK(α) controls canonical TGF(ß)-SMAD signaling to regulate genes expressing SNAIL and SLUG during EMT in panc1 cells
    Martina Brandl
    II Medizinische Klinik, Technische Universitat Munchen, Ismaninger Strasse 22, 81675 Munchen, Germany
    J Cell Sci 123:4231-9. 2010
    ..Taken together, these findings indicate that IKKα contributes to the tumor-promoting function of the TGFβ-SMAD signaling pathway in particular cancers...
  74. ncbi Identification and characterization of an IkappaB kinase
    C H Regnier
    Tularik, Inc, South San Francisco, California 94080, USA
    Cell 90:373-83. 1997
    ..This phosphorylation of IkappaB-alpha is greatly enhanced by NIK costimulation. Thus, CHUK is a NIK-activated IkappaB-alpha kinase that links TNF- and IL-1-induced kinase cascades to NF-kappaB activation...
  75. ncbi The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation
    E Zandi
    Department of Pharmacology, University of California at San Diego, La Jolla 92093 0636, USA
    Cell 91:243-52. 1997
    ..While the interactions between IKKalpha and IKKbeta may be mediated through their leucine zipper motifs, their helix-loop-helix motifs may be involved in interactions with essential regulatory subunits...
  76. ncbi Tumor necrosis factor receptor-associated factors (TRAFs)--a family of adapter proteins that regulates life and death
    R H Arch
    Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, Illinois 60637 USA
    Genes Dev 12:2821-30. 1998
  77. ncbi IKAP is a scaffold protein of the IkappaB kinase complex
    L Cohen
    Tularik Inc, South San Francisco, California 94080, USA
    Nature 395:292-6. 1998
    ..We show that IKAP is a scaffold protein and a regulator for three different kinases involved in pro-inflammatory cytokine signalling...
  78. pmc Activation of IkappaB kinase beta by protein kinase C isoforms
    M J Lallena
    Laboratorio Glaxo Wellcome CSIC de Biología Molecular y Celular, Centro de Biología Molecular Severo Ochoa Consejo Superior de Investigaciones Científicas Universidad Autónoma de Madrid, Universidad Autonoma, 28049 Madrid, Spain
    Mol Cell Biol 19:2180-8. 1999
    ..Collectively, these results demonstrate a critical role for the PKC isoforms in the NF-kappaB pathway at the level of IKKbeta activation and IkappaB degradation...
  79. ncbi NF-kappaB activation by tumour necrosis factor requires the Akt serine-threonine kinase
    O N Ozes
    Department of Microbiology and Immunology, Indiana University School of Medicine, The Walther Oncology Center, Indianapolis 46202, USA
    Nature 401:82-5. 1999
    ..Mutation of this amino acid blocks phosphorylation by Akt or TNF and activation of NF-kappaB. These findings indicate that Akt is part of a signalling pathway that is necessary for inducing key immune and inflammatory responses...
  80. pmc Mixed-lineage kinase 3 delivers CD3/CD28-derived signals into the IkappaB kinase complex
    S P Hehner
    Department of Immunochemistry, German Cancer Research Center, 69120 Heidelberg, Germany
    Mol Cell Biol 20:2556-68. 2000
    ..A dominant negative version of MLK3 inhibited NF-kappaB- and CD28RE/AP-dependent transcription elicited by the Rho family GTPases Rac and Cdc42, thereby providing a novel link between these GTPases and the IKC...
  81. ncbi Selective inhibition of NF-kappaB activation by a peptide that blocks the interaction of NEMO with the IkappaB kinase complex
    M J May
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Science 289:1550-4. 2000
    ..The NBD provides a target for the development of drugs that would block proinflammatory activation of the IKK complex without inhibiting basal NF-kappaB activity...
  82. ncbi TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90
    Guoqing Chen
    Tularik, Incorporated, Two Corporate Drive, South San Francisco, CA 94080, USA
    Mol Cell 9:401-10. 2002
    ..Therefore, heterocomplex formation with Cdc37/Hsp90 is a prerequisite for TNF-induced activation and trafficking of IKK from the cytoplasm to the membrane...
  83. ncbi NEMO trimerizes through its coiled-coil C-terminal domain
    Fabrice Agou
    Unité de Régulation Enzymatique des Activités Cellulaires, Paris Cedex 15, France
    J Biol Chem 277:17464-75. 2002
    ..We propose a model in which the activation of the IKK complex occurs through the trimerization of NEMO upon binding to a not yet identified upstream activator...
  84. ncbi Histone H3 phosphorylation by IKK-alpha is critical for cytokine-induced gene expression
    Yumi Yamamoto
    Division of Hematology Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8594, USA
    Nature 423:655-9. 2003
    ..These results define a new nuclear role of IKK-alpha in modifying histone function that is critical for the activation of NF-kappaB-directed gene expression...
  85. ncbi Protein phosphatase 2Cbeta association with the IkappaB kinase complex is involved in regulating NF-kappaB activity
    Shashi Prajapati
    Division of Hematology Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 8594, USA
    J Biol Chem 279:1739-46. 2004
    ..These studies are consistent with the ability of PP2Cbeta to down-regulate cytokine-induced NF-kappaB activation by altering IKK activity...
  86. ncbi Nuclear role of I kappa B Kinase-gamma/NF-kappa B essential modulator (IKK gamma/NEMO) in NF-kappa B-dependent gene expression
    Udit N Verma
    Division of Hematology Oncology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8594, USA
    J Biol Chem 279:3509-15. 2004
    The I kappa B kinase (IKK) complex, which is composed of the two kinases IKK alpha and IKK beta and the regulatory subunit IKK gamma/nuclear factor-kappa B (NF-kappa B) essential modulator (NEMO), is important in the cytokine-induced ..
  87. ncbi IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a
    Mickey C T Hu
    Department of Molecular and Cellular Oncology, The University of Texas, Houston, TX 77030, USA
    Cell 117:225-37. 2004
    ..These results suggest the negative regulation of FOXO factors by IKK as a key mechanism for promoting cell growth and tumorigenesis...
  88. pmc The IkappaB kinase complex and NF-kappaB act as master regulators of lipopolysaccharide-induced gene expression and control subordinate activation of AP-1
    Daniel Krappmann
    Max Delbruck Center for Molecular Medicine, Berlin, Germany
    Mol Cell Biol 24:6488-500. 2004
    ..Thus, our data illustrate that NF-kappaB orchestrates immediate-early effects of LPS signaling and controls secondary AP-1 activation to mount an appropriate biological response...
  89. ncbi Constitutive nuclear expression of the I kappa B kinase complex and its activation in human neutrophils
    Thornin Ear
    Pulmonary Division, Faculty of Medicine, Universite de Sherbrooke, Sherbrooke, Quebec, Canada
    J Immunol 175:1834-42. 2005
    ..More importantly, our findings unveil a hitherto unsuspected mode of activation for the IKK/IkappaB signaling cascade within the cell nucleus...
  90. pmc A critical role for I kappaB kinase alpha in the development of human and mouse squamous cell carcinomas
    Bigang Liu
    Department of Carcinogenesis, University of Texas M D Anderson Cancer Center, Smithville, TX 78957, USA
    Proc Natl Acad Sci U S A 103:17202-7. 2006
    ..Thus, overexpression of IKKalpha in the epidermis antagonized chemical carcinogen-induced mitogenic and angiogenic activities, repressing tumor progression and metastases...
  91. ncbi IKKalpha regulates the mitotic phase of the cell cycle by modulating Aurora A phosphorylation
    Shashi Prajapati
    Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, Indiana 46285, USA
    Cell Cycle 5:2371-80. 2006
    ..Taken together, these data provide the evidence that IKKalpha regulates the M phase of the cell cycle by modulating Aurora A phosphorylation and activation leading to the regulation of the M phase of the cell cycle...
  92. pmc Retroviral oncoprotein Tax deregulates NF-kappaB by activating Tak1 and mediating the physical association of Tak1-IKK
    Xuefeng Wu
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, Hershey Medical Center, PO Box 850, Hershey, Pennsylvania 17033, USA
    EMBO Rep 8:510-5. 2007
    ..These findings show a pathological mechanism of IKK activation by Tax and provide an example for how IKK is persistently activated in cancer cells...
  93. pmc Phosphorylation of CBP by IKKalpha promotes cell growth by switching the binding preference of CBP from p53 to NF-kappaB
    Wei Chien Huang
    Department of Pharmacology, College of Medicine, National Taiwan University, Taipei 10018, Taiwan Department of Molecular and Cellular Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Mol Cell 26:75-87. 2007
    ..Our results suggest that phosphorylation of CBP by IKKalpha regulates the CBP-mediated crosstalk between NF-kappaB and p53 and thus may be a critical factor in the promotion of cell proliferation and tumor growth...
  94. ncbi Stabilization of p73 by nuclear IkappaB kinase-alpha mediates cisplatin-induced apoptosis
    Kazushige Furuya
    Division of Biochemistry, Chiba Cancer Center Research Institute, Chiba 260 8717, Japan
    J Biol Chem 282:18365-78. 2007
    ....
  95. pmc Akt-dependent regulation of NF-{kappa}B is controlled by mTOR and Raptor in association with IKK
    Han C Dan
    Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA
    Genes Dev 22:1490-500. 2008
    ..The results provide insight into the effects of Akt/mTOR-dependent signaling on gene expression and into the therapeutic action of rapamycin...
  96. doi Notch-1 associates with IKKalpha and regulates IKK activity in cervical cancer cells
    L L Song
    Breast Cancer Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153, USA
    Oncogene 27:5833-44. 2008
    ..Our data indicate that Notch-1 regulates NF-kappaB in cervical cancer cells at least in part via cytoplasmic and nuclear IKK-mediated pathways...
  97. pmc RelB is differentially regulated by IkappaB Kinase-alpha in B cells and mouse lung by cigarette smoke
    Se Ran Yang
    Department of Environmental Medicine, University of Rochester Medical Center, Box 850, 601 Elmwood Ave, Rochester, NY 14642, USA
    Am J Respir Cell Mol Biol 40:147-58. 2009
    ..Rapid degradation of RelB signals for RelA/p65 activation and loss of its protective ability to suppress the proinflammatory cytokine release in lymphoid B cells...
  98. pmc IKKalpha, a critical regulator of epidermal differentiation and a suppressor of skin cancer
    Pascal Descargues
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, Cancer Center, School of Medicine, University of California, San Diego, La Jolla, CA 92093 0723, USA
    EMBO J 27:2639-47. 2008
    ..Although these are not the only functions of nuclear IKKalpha, this multifunctional protein is a key regulator of keratinocyte and epidermal differentiation and a critical suppressor of skin cancer...
  99. pmc The IKK complex contributes to the induction of autophagy
    Alfredo Criollo
    INSERM, U848, Villejuif, France
    EMBO J 29:619-31. 2010
    ..Altogether, these results indicate that IKK has a cardinal role in the stimulation of autophagy by physiological and pharmacological stimuli...
  100. doi Constitutive association of TGF-beta-activated kinase 1 with the IkappaB kinase complex in the nucleus and cytoplasm of human neutrophils and its impact on downstream processes
    Thornin Ear
    Pulmonary Division, Faculty of Medicine, Université de Sherbrooke and Centre de Recherche du CHUS, Sherbrooke, Quebec, Canada
    J Immunol 184:3897-906. 2010
    ....
  101. pmc IKKα activation of NOTCH links tumorigenesis via FOXA2 suppression
    Mo Liu
    Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Mol Cell 45:171-84. 2012
    ..Here, we report a TNFα/IKKα/FOXA2/NUMB/NOTCH1 pathway that is critical for inflammation-mediated tumorigenesis and may provide a target for clinical intervention in human cancer...

Research Grants49

  1. Role of IKK in NSCLC: Modulation of SMRT and NF-kappaB
    Marty W Mayo; Fiscal Year: 2012
    ..NF-?B stimulates gene expression of PRC proteins by recruiting IKK1 and PCAF to responsive promoters and derepressing SMRT (silencing mediator for retinoid and thyroid hormone ..
  2. Negative regulation of NF-kB and inflammation by TAX1BP1
    Edward W Harhaj; Fiscal Year: 2012
    ..Finally, we have demonstrated that TAX1BP1 undergoes IKKa-dependent phosphorylation in response to proinflammatory signals...
  3. ALBERT SIDNEY BALDWIN; Fiscal Year: 2014
    ..Importantly, loss of RelA/p65 leads to apoptosis in these Ras-transformed cells. In vitro data indicate that IKKa and [unreadable], upstream regulators of NF-?B, and Aurora kinase control the ability of oncogenic Ras mutants to ..
  4. David C Parker; Fiscal Year: 2015
    ..Inhibition of this pathway by drugs acting specifically on enzymes in this pathway (IKK1 and/or NIK) has the potential to block ongoing immune reactions that are dependent on internal danger signals ..
  5. The Role of IKK and NF-kappaB in Controlling mTOR Signaling and TSC Progression
    Hancai Dan; Fiscal Year: 2012
    ..I will characterize the mechanism whereby IKK1 controls TORC1 and mTORC2 activity in several cancer cells and in TSC2 -/- MEF cells...
  6. ALBERT SIDNEY BALDWIN; Fiscal Year: 2014
    ..Additionally, we explore the control of Akt in these cells through an IKK1-mTORC2 mechanism...
  7. Structural and functional studies of the IkappaB kinase (IKK) complex
    Hao Wu; Fiscal Year: 2013
    ..The I?B kinase (IKK), comprising IKKa and IKK[unreadable], is at the heart of NF-?B activation and mediates two NF-?B activation pathways...
  8. IKKa-Dependent Negative Feedback Control of Non-Canonical NF-kB Activation
    Genhong Cheng; Fiscal Year: 2012
    ..Our preliminary studies have demonstrated that IKK1, activated by NIK, can induce not only p100 phosphorylation and processing but also phosphorylation and ..
  9. Mechanisms for Hormone-Dependent NF-kB Activation
    Allan Brasier; Fiscal Year: 2007
    ..3. To determine the relationship of the TAKI-IKKa signaling pathway on AII-and NIK-induced NF-kappaB activation...
  10. Sanjay Gupta; Fiscal Year: 2014
    ..In this renewal application, we hypothesize that I(B kinase: IKKa/[unreadable] acts as a central hub in mediating the anticancer effects of apigenin on multiple signal transduction ..
  11. MECHANISMS OF CHONDROPROTECTION BY POMEGRANATE FRUIT EXTRACT
    Tariq M Haqqi; Fiscal Year: 2011
    ..activation of NF-KB by modulating the activation of kinases upstream of kB (inhibitor of NF-KB) including IKKa and IKK(3 (Specific Aim 2);whether PFE inhibit the IL-1(3-induced oxidative stress and dedifferentiation of human ..
  12. Yong Jun Liu; Fiscal Year: 2014
    ..of TLR9 by CpG-A oligodeoxynucleotide (ODN) in the early endosomes preferentially triggers the TRAF3/IRAK1/IKK1/PI3K/IRF7 signal cascade leading to type 1 IFN responses, whereas engagement of TLR9 by CpG-B ODN in the late ..
  13. Yousef Abu-Amer; Fiscal Year: 2016
    ..The former pathway requires assembly of large IKK complex encompassing IKK1, IKK2, and IKK?, also known as NEMO...
  14. Evaluation of NBD Peptides as an Adjunct Therapy for the Treatment of Non-Hodgkin
    PATRICK MICHAEL FLOOD; Fiscal Year: 2010
    ..NBD peptide inhibits both IKKa and IKK[unreadable] activity and efficiently blocks classical, NEMO dependent NF-?B activation...
  15. Effect of high fat diet on pancreatic cancer in IKKa deficient mice
    Ning Li; Fiscal Year: 2013
    ....
  16. Mechanisms of Reovirus-Induced Apoptosis
    Terence S Dermody; Fiscal Year: 2011
    ..Mice lacking IKKa, IKK(3, or NF-KB p50 in either the brain or heart will be infected with reovirus and assessed for apoptosis and ..
  17. Michael Karin; Fiscal Year: 2016
    ..the role of p62 accumulation in enhanced tumorigenesis in Ikk[unreadable]?pan mice;5) how haploinsufficiency for IKKa results in PanIN lesion development upon HFD consumption and whether prolonged obesity causes eventual PanCa ..
  18. SCOTT DONALD WEATHERBEE; Fiscal Year: 2015
    ..For example, Ikk1 and stratifin, appear to have similar developmental roles as shd and have been implicated in tumorigenesis...
  19. Jun Li Luo; Fiscal Year: 2015
    ..B cells, which produce LTa:[unreadable] heterotrimers that stimulate LT[unreadable]R on PCa cells to induce IKKa nuclear translocation and activation, thereby enhancing androgen-independent growth...
  20. Assay Development for Screening of Specific IKKalpha Kinase Inhibitors
    Jun Li Luo; Fiscal Year: 2011
    DESCRIPTION (provided by applicant): Although IKK1 and IKK2 are highly homologous, their functions are very unique...
  21. Design of Macrocyclic Inhibitors of the NEMO/IKKa/b Protein-Protein Interaction
    Adrian Whitty; Fiscal Year: 2013
    ..Inhibiting this pathway represents a promising new approach for the development of effective drugs and, consequently, is highly relevant to public health. ..
  22. Macrophage Akt and IKKalpha signaling in apoptosis and atherosclerosis
    Macrae F Linton; Fiscal Year: 2013
    ..Interestingly, Akt has been reported to mediate signaling through IKKa that may activate the NF-kB pathways with its anti-apoptotic activity...
  23. IkB Kinase alpha (IKKalpha): Role in Skin Carcinogenesis
    Yinling Hu; Fiscal Year: 2007
    ..Therefore, loss of IKKa not only interferes with keratinocyte differentiation but also permits or causes neoplastic transformation...
  24. Mechanisms of IkappaB Kinase Regulation
    Ebrahim Zandi; Fiscal Year: 2006
    ..A multi component complex consisting of alpha, beta, and gamma subunits. IKKa and IKKb are the catalytic kinase subunits, which form homo-and heterodimers...
  25. Role of IKK signaling in skeletal muscle atrophy
    Darin Van Gammeren; Fiscal Year: 2007
    ..IKKB operates in a complex with IKKalpha (IKKa) and gamma...
  26. NFKB AND APOPTOSIS REGULATORY COMPLEXES
    EMAD ALNEMRI; Fiscal Year: 2004
    ..Apaf 1 caspase 9 pathway and activate NFKB by acting upstream of the NFKB inducing kinase, NIK, and the IKB kinase, IKKa. Deletion of either the CARD or the CTD domain inhibits both activities...
  27. ANTI APOPTOTIC SIGNALING IN MYELOMA--BCL 2 AND NF KAPPA
    Rena Feinman; Fiscal Year: 2002
    ..There studies will hopefully provide deeper insight into the molecular basis of drug resistance in MM and should result in the identification of potential targets for therapeutic intervention. ..
  28. The Role of Regulation of FOXO3a in Tumor Suppression
    Mickey C T Hu; Fiscal Year: 2010
    ..The novel observations that IKKa and IKKy function in the nucleus to regulate NF-icB activity and that IKKp regulates nuclear extrusion of FOXOSa ..
  29. REGULATION OF NF-KAPPA B
    Inder Verma; Fiscal Year: 2009
    ..We plan to understand the molecular function of the two kinases, IKK1 and IKK2 present in the IKK complex because they phosphorylate iKBcc at unique residues to trigger its degradation ..
  30. Functions and Mechanisms of Radiation Induced Responses
    Michael Karin; Fiscal Year: 2006
    ..abstract_text> ..
  31. IGFS & IGF-BINDING PROTEINS IN GROWTH & DIFFERENTIATION
    Pomila Singh; Fiscal Year: 2002
    ....
  32. REGULATION OF XENOBIOTIC-METABOLIZING CYP3A
    Richard Zangar; Fiscal Year: 2002
    ....
  33. AUTOCRINE ROLE OF GASTRIN-LIKE PEPTIDES IN COLON CANCER
    Pomila Singh; Fiscal Year: 2002
    ..If we are successful in purifying the novel GP-R (and confirm its role in mediating the mitogenic effects of gastrins) then one can develop systemic strategies to block the receptor mediated effects in future funding periods. ..
  34. Picking and Gridding Q Bot System
    Joseph DiDonato; Fiscal Year: 2003
    ....
  35. FLOW SHEAR INDUCED NF-KB MEDIATED REGULATION
    Sumathy Mohan; Fiscal Year: 2003
    ..Understanding of NF- kappaB signaling mechanisms in VCAM-1 regulation can also be applied to other inflammatory conditions. ..
  36. How Anthrax lethal factor kills activated macrophages
    Michael Karin; Fiscal Year: 2003
    ..anthracis and its host, this project should enable the design of new therapeutic strategies that will tilt the balance in favor of the host macrophage in the battle against B. anthracis and inhalation anthrax. ..
  37. Apoptotic Mechanisms of Tocotrienols in Mammary Cancer
    Paul Sylvester; Fiscal Year: 2004
    ..Although caspase-8 activation is associated with death receptor signaling, the exact receptor/ligand signaling mechanism(s) mediating tocotrienol-induced caspase-8 activation has not been determined. ..
  38. INFLAMMATION--IKAPPA B KINASE STRUCTURE FUNCTION STUDIES
    Joseph DiDonato; Fiscal Year: 2004
    ..These pharmaceuticals will be of great medical benefit in combating diseases of a acute and chronic inflammation, which can lead to cancer. ..
  39. Chemokines, nitric oxide, and myocardial depression
    Bysani Chandrasekar; Fiscal Year: 2005
    ..The results from these studies will further our knowledge of chemokine biology and lead to new therapeutic strategies to prevent or treat myocardial dysfunction in ischemia-reperfusion injury. ..
  40. Diet and Risk of Ovarian Cancer
    Ellen Chang; Fiscal Year: 2005
    ..The results of the proposed analyses will provide further understanding of the etiology of ovarian cancer. ..
  41. Amelioration of Uveitis by Aldose reductase Inhibition
    KOTA VENKATA RAMANA; Fiscal Year: 2010
    ..abstract_text> ..
  42. Immunogenetics of Non-Hodgkin Lymphoma Survival
    James Cerhan; Fiscal Year: 2006
    ..abstract_text> ..
  43. INTERACTIONS OF HEAVY METAL IONS WITH THE HUMAN GENOME
    Michael Karin; Fiscal Year: 2007
    ..As NF-KB plays a key role in inflammation, understanding the regulation of IKK activity by oxidants, such as ozone, will provide a molecular basis for oxidant induced inflammatory disease. ..
  44. Using gene targeting to address the role of LRRK2 in Parkinson's disease
    Bruce Hostager; Fiscal Year: 2007
    ..This knowledge will aid in the identification of the environmental triggers and additional genetic factors that participate in the development of Parkinson's disease. ..
  45. Aspirin use, genetic variation in aspirin related-genes, and Hodgkin lymphoma ris
    Ellen Chang; Fiscal Year: 2007
    ..Our specific aims are to answer whether genetic variation in 1.) NFKB1/p105, NFKBIA, and/or IKKA/CHUK (genes involved in NF-kB activation and inhibition); 2...
  46. How Anthrax lethal factor kills macrophages
    Michael Karin; Fiscal Year: 2008
    ..Interference with this activation process may be used to increase host resistance to bacterial infections, both with agents of bioterrorism and more common pathogens. ..
  47. Bioinformatics for Protein Microarrays
    Richard Zangar; Fiscal Year: 2009
    ....
  48. Growth Factors, Curcumin and Colon Carcinogenesis
    Pomila Singh; Fiscal Year: 2010
    ..The results of these studies are expected to help in developing mechanism-based strategies for preventative/treatment protocols for CRCusing curcumin like agents. ..
  49. Molecular Epidemiology of non-Hodgkin Lymphoma Survival
    James R Cerhan; Fiscal Year: 2010
    ..Host genetics may also lead to a better understanding of NHL pathophysiology that could lead to new approaches to improve the survival of NHL patients. ..