IKKgamma

Summary

Gene Symbol: IKKgamma
Description: inhibitor of nuclear factor kappa B kinase subunit gamma
Alias: AMCBX1, FIP-3, FIP3, Fip3p, IKK-gamma, IKKAP1, IKKG, IMD33, IP1, IP2, IPD2, NEMO, ZC2HC9, NF-kappa-B essential modulator, I-kappa-B kinase subunit gamma, NF-kappa-B essential modifier, ikB kinase subunit gamma, ikB kinase-associated protein 1, incontinentia pigmenti, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma
Species: human

Top Publications

  1. ncbi A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations
    S Aradhya
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Hum Mol Genet 10:2171-9. 2001
  2. ncbi Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain
    L Deng
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas 75390, USA
    Cell 103:351-61. 2000
  3. 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
  4. doi Annexin-1 interacts with NEMO and RIP1 to constitutively activate IKK complex and NF-κB: implication in breast cancer metastasis
    P Bist
    Department of Physiology and NUS Immunology Program, Inflammation and Cancer Lab, National University of Singapore
    Oncogene 30:3174-85. 2011
  5. ncbi The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination
    Andrew Kovalenko
    Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel
    Nature 424:801-5. 2003
  6. pmc Endotoxin tolerance impairs IL-1 receptor-associated kinase (IRAK) 4 and TGF-beta-activated kinase 1 activation, K63-linked polyubiquitination and assembly of IRAK1, TNF receptor-associated factor 6, and IkappaB kinase gamma and increases A20 expression
    Yanbao Xiong
    Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    J Biol Chem 286:7905-16. 2011
  7. 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
  8. pmc Structural basis for recognition of diubiquitins by NEMO
    Yu Chih Lo
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10021, USA
    Mol Cell 33:602-15. 2009
  9. pmc Signal processing by its coil zipper domain activates IKK gamma
    Stuart Bloor
    Division of Protein and Nucleic Acid Chemistry, Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
    Proc Natl Acad Sci U S A 105:1279-84. 2008
  10. doi Ubiquitin binding mediates the NF-kappaB inhibitory potential of ABIN proteins
    S Wagner
    Institute for Biochemistry II, Goethe University Medical School, Frankfurt, Germany
    Oncogene 27:3739-45. 2008

Research Grants

Detail Information

Publications259 found, 100 shown here

  1. ncbi A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations
    S Aradhya
    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Hum Mol Genet 10:2171-9. 2001
    b>Incontinentia pigmenti (IP) is an X-linked dominant disorder characterized by abnormal skin pigmentation, retinal detachment, anodontia, alopecia, nail dystrophy and central nervous system defects...
  2. ncbi Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain
    L Deng
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas 75390, USA
    Cell 103:351-61. 2000
    ..These results unveil a new regulatory function for ubiquitin, in which IKK is activated through the assembly of K63-linked polyubiquitin chains...
  3. 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
    ..Bcl10 overexpression is sufficient to activate NF-kappaB, a process that requires the NF-kappaB essential modulator NEMO (also known as IKK-gamma), which is the regulatory subunit of the IkappaB kinase complex...
  4. doi Annexin-1 interacts with NEMO and RIP1 to constitutively activate IKK complex and NF-κB: implication in breast cancer metastasis
    P Bist
    Department of Physiology and NUS Immunology Program, Inflammation and Cancer Lab, National University of Singapore
    Oncogene 30:3174-85. 2011
    ..and NF-κB signaling pathway, and immunoprecipitation confirmed that ANXA1 can bind to and interact with IKKγ or NEMO, but not IKKα or IKKβ...
  5. ncbi The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination
    Andrew Kovalenko
    Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel
    Nature 424:801-5. 2003
    ..Here we report that CYLD, a tumour suppressor that is mutated in familial cylindromatosis, interacts with NEMO, the regulatory subunit of IKK...
  6. pmc Endotoxin tolerance impairs IL-1 receptor-associated kinase (IRAK) 4 and TGF-beta-activated kinase 1 activation, K63-linked polyubiquitination and assembly of IRAK1, TNF receptor-associated factor 6, and IkappaB kinase gamma and increases A20 expression
    Yanbao Xiong
    Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    J Biol Chem 286:7905-16. 2011
    ....
  7. 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...
  8. pmc Structural basis for recognition of diubiquitins by NEMO
    Yu Chih Lo
    Department of Biochemistry, Weill Cornell Medical College, New York, NY 10021, USA
    Mol Cell 33:602-15. 2009
    b>NEMO is the regulatory subunit of the IkappaB kinase (IKK) in NF-kappaB activation, and its CC2-LZ region interacts with Lys63 (K63)-linked polyubiquitin to recruit IKK to receptor signaling complexes...
  9. pmc Signal processing by its coil zipper domain activates IKK gamma
    Stuart Bloor
    Division of Protein and Nucleic Acid Chemistry, Structural Studies Division, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom
    Proc Natl Acad Sci U S A 105:1279-84. 2008
    ..Activity of IKK is governed by its noncatalytic subunit IKKgamma. Signaling defects due to missense mutations in IKKgamma have been correlated to its inability to either become ..
  10. doi Ubiquitin binding mediates the NF-kappaB inhibitory potential of ABIN proteins
    S Wagner
    Institute for Biochemistry II, Goethe University Medical School, Frankfurt, Germany
    Oncogene 27:3739-45. 2008
    ..Moreover, this region is also present in NF-kappaB essential modulator/IkappaB kinase gamma (NEMO/IKKgamma) and the NEMO-like protein optineurin, and is therefore termed UBD in ABIN proteins and NEMO (UBAN)...
  11. doi Human T-cell leukemia virus type 1 bZIP factor selectively suppresses the classical pathway of NF-kappaB
    Tiejun Zhao
    Laboratory of Virus Control, Institute for Virus Research, Kyoto University, Kyoto, Japan
    Blood 113:2755-64. 2009
    ..Selective suppression of the classical NF-kappaB pathway by HBZ renders the alternative NF-kappaB pathway predominant after activation of NF-kappaB by Tax or other stimuli, which might be critical for oncogenesis...
  12. pmc Polyubiquitin binding to optineurin is required for optimal activation of TANK-binding kinase 1 and production of interferon β
    Catherine E Gleason
    Medical Research Council Protein Phosphorylation Unit, The Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    J Biol Chem 286:35663-74. 2011
    ..Previously, we identified the NF-κB essential modulator (NEMO)-related polyubiquitin-binding protein, optineurin (OPTN), as a novel binding partner of TBK1...
  13. 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
    b>NEMO/IkappaB kinase (IKK) gamma is the regulatory component of the IKK complex comprising the two protein kinases, IKKalpha and IKKbeta...
  14. ncbi Constitutive activation of TAK1 by HTLV-1 tax-dependent overexpression of TAB2 induces activation of JNK-ATF2 but not IKK-NF-kappaB
    Shunsuke Suzuki
    Division of Pathogenic Biochemistry, Institute of Natural Medicine, University of Toyama, Toyama 930 0194, Japan
    J Biol Chem 282:25177-81. 2007
    ..These results indicate that Tax-mediated TAK1 activation is important for the activation of ATF2 rather than NF-kappaB...
  15. pmc LUBAC regulates NF-κB activation upon genotoxic stress by promoting linear ubiquitination of NEMO
    Jixiao Niu
    Department of Pathology and Laboratory Medicine, Center for Cancer Research, Memphis, TN, USA
    EMBO J 30:3741-53. 2011
    ..The NF-κB essential modulator (NEMO/IKKγ) is indispensable for NF-κB activation by diverse stimuli including genotoxic stress...
  16. ncbi Sequential modification of NEMO/IKKgamma by SUMO-1 and ubiquitin mediates NF-kappaB activation by genotoxic stress
    Tony T Huang
    Department of Pharmacology, University of Wisconsin Madison, 301 SMI, 1300 University Avenue, Madison, WI 53706, USA
    Cell 115:565-76. 2003
    ..Central to NF-kappaB signaling pathways is NEMO/IKKgamma, the regulatory subunit of the cytoplasmic IkappaB kinase (IKK) complex...
  17. pmc Identification of a cell protein (FIP-3) as a modulator of NF-kappaB activity and as a target of an adenovirus inhibitor of tumor necrosis factor alpha-induced apoptosis
    Y Li
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 96:1042-7. 1999
    ..Because the activation of NF-kappaB has been shown to inhibit apoptosis, FIP-3 appears both to activate a cell-death pathway and to inhibit an NF-kappaB-dependent survival mechanism...
  18. 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
    ..The core IKK consists of two catalytic serine kinases, IKKalpha and IKKbeta, and a noncatalytic subunit, IKKgamma. IKKgamma is required for IKK activity by mediating kinase oligomerization and serving to couple the core ..
  19. pmc NEMO binds ubiquitinated TANK-binding kinase 1 (TBK1) to regulate innate immune responses to RNA viruses
    Lingyan Wang
    Department of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, United States of America
    PLoS ONE 7:e43756. 2012
    ..Ubiquitinated TBK1 recruits the downstream adaptor NEMO through ubiquitin binding domains...
  20. ncbi In vivo identification of inducible phosphoacceptors in the IKKgamma/NEMO subunit of human IkappaB kinase
    Robert S Carter
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232 0295, USA
    J Biol Chem 278:19642-8. 2003
    ..two structurally related catalytic subunits termed IKKalpha and IKKbeta as well as a noncatalytic subunit called IKKgamma/NEMO...
  21. ncbi Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-kappaB activation
    Francesca Fusco
    Institute of Genetics and Biophysics, Adriano Buzzati Traverso CR, Naples, Italy
    Hum Mol Genet 13:1763-73. 2004
    b>Incontinentia Pigmenti (IP) is an X-linked genodermatosis that is lethal for males and present in females with abnormal skin pigmentation and high variable clinical signs, including retinal detachment, anodontia, alopecia, nail dystrophy ..
  22. 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...
  23. ncbi Ubiquitination of RIP is required for tumor necrosis factor alpha-induced NF-kappaB activation
    Hongxiu Li
    Deptartment of Molecular and Cellular Oncology, University of Texas, M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 281:13636-43. 2006
    ..Together, our studies provide the first genetic evidence that the ubiquitination of RIP is required for TNFalpha-induced NF-kappaB activation...
  24. pmc HSV ICP0 recruits USP7 to modulate TLR-mediated innate response
    Sandrine Daubeuf
    Institut de Pharmacologie et de Biologie Structurale, Centre National de Recherche Scientifique CNRS, Unité Mixte de Recherche 5089, Toulouse, France
    Blood 113:3264-75. 2009
    ..Cytoplasmic USP7 binds to and deubiquitinates TRAF6 and IKKgamma, thus terminating TLR-mediated NF-kappaB and JNK activation...
  25. doi Flotillin-1 promotes tumor necrosis factor-α receptor signaling and activation of NF-κB in esophageal squamous cell carcinoma cells
    Libing Song
    State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Cancer Center, Sun Yat Sen University, Guangzhou, Guangdong, China
    Gastroenterology 143:995-1005.e12. 2012
    ..We investigated the role of FLOT1 signaling and activation of the transcription factor nuclear factor (NF)-κB in esophageal squamous cell carcinoma (ESCC) cells...
  26. 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...
  27. 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
    ..to a approximately 700-kDa IkappaB kinase (IKK) complex and physically associates with IKKalpha, IKKbeta, NEMO/IKKgamma, and RIP...
  28. ncbi Tax ubiquitylation and sumoylation control critical cytoplasmic and nuclear steps of NF-kappaB activation
    Rihab Nasr
    Department of Internal Medicine, American University of Beirut, PO Box 113 6044, Beirut, Lebanon
    Blood 107:4021-9. 2006
    ..Thus, ubiquitylation and sumoylation of the same residues of Tax regulate 2 essential steps controlling NF-kappaB activation, demonstrating how these posttranslational modifications can cooperate to promote Tax-induced transformation...
  29. ncbi The NEMO adaptor bridges the nuclear factor-kappaB and interferon regulatory factor signaling pathways
    Tiejun Zhao
    Terry Fox Molecular Oncology Group, Lady Davis Institute for Medical Research, McGill University, Montreal H3T 1E2, Canada
    Nat Immunol 8:592-600. 2007
    ..Here we demonstrate that virus-induced activation of IRF3 and IRF7 depended on the NF-kappaB modulator NEMO, which acted 'upstream' of the kinases TBK1 and IKKepsilon...
  30. 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
    ..We also show that IL-1 triggers the interaction of K63-pUb-IRAK1 with NEMO, a regulatory subunit of the IkappaBalpha kinase (IKK) complex, but not with the NEMO[D311N] mutant that cannot ..
  31. doi Biochemical aspects of the neuroprotective mechanism of PTEN-induced kinase-1 (PINK1)
    Ryan D Mills
    Department of Biochemistry and Molecular Biology, Bio21 Institute of Molecular Science and Biotechnology, University of Melbourne, Parkville, Victoria, Australia
    J Neurochem 105:18-33. 2008
    ..This model may serve as a conceptual framework for future investigation into the molecular basis of PD pathogenesis...
  32. pmc NEMO specifically recognizes K63-linked poly-ubiquitin chains through a new bipartite ubiquitin-binding domain
    E Laplantine
    Unite de Signalisation Moleculaire et Activation Cellulaire, Institut Pasteur, URA 2582 CNRS, Paris, France
    EMBO J 28:2885-95. 2009
    An important property of NEMO, the core element of the IKK complex involved in NF-kappaB activation, resides in its ability to specifically recognize poly-ubiquitin chains...
  33. pmc The scaffold protein TANK/I-TRAF inhibits NF-kappaB activation by recruiting polo-like kinase 1
    Wanqiao Zhang
    State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 102206, China
    Mol Biol Cell 21:2500-13. 2010
    ..PLK1 is bound to NEMO (IKKgamma) through TANK to form a ternary complex in vivo...
  34. pmc NRP/Optineurin Cooperates with TAX1BP1 to potentiate the activation of NF-kappaB by human T-lymphotropic virus type 1 tax protein
    Chloé Journo
    Unité d Epidémiologie et Physiopathologie des Virus Oncogènes, CNRS URA 3015, Institut Pasteur, Paris, France
    PLoS Pathog 5:e1000521. 2009
    ..of NF-kappaB occurs predominantly in the cytoplasm, where Tax1 binds NF-kappaB Essential Modulator (NEMO/IKKgamma) and triggers the activation of IkappaB kinases...
  35. pmc Epstein-Barr latent membrane protein 1 transformation site 2 activates NF-kappaB in the absence of NF-kappaB essential modifier residues 133-224 or 373-419
    Daniela Boehm
    Department of Medicine, Division of Infectious Diseases, Brigham and Women s Hospital, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 107:18103-8. 2010
    ..TES2 principally activates canonical NF-κB, which we confirm is NF-κB essential modifier (NEMO)-dependent and requires an intact ubiquitin binding in A20 binding inhibitor of NF-κB and NEMO (UBAN) domain...
  36. pmc MCP-induced protein 1 deubiquitinates TRAF proteins and negatively regulates JNK and NF-kappaB signaling
    Jian Liang
    Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA
    J Exp Med 207:2959-73. 2010
    ..Sequence analysis together with serial mutagenesis defined a deubiquitinating enzyme domain and a ubiquitin association domain in MCPIP1. Our results indicate that MCPIP1 is a critical modulator of inflammatory signaling...
  37. doi Distinct roles of Rab11 and Arf6 in the regulation of Rab11-FIP3/arfophilin-1 localization in mitotic cells
    Senye Takahashi
    Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo ku, Japan
    Genes Cells 16:938-50. 2011
    ..Furthermore, FIP3 undergoes dynamic redistribution to the intercellular bridge during cytokinesis...
  38. pmc The cytoplasmic domain of the HIV-1 glycoprotein gp41 induces NF-κB activation through TGF-β-activated kinase 1
    Thomas S Postler
    New England Primate Research Center, Department of Microbiology and Molecular Genetics, Harvard Medical School, Southborough, MA 01772 9102, USA
    Cell Host Microbe 11:181-93. 2012
    ..These findings demonstrate an evolutionarily conserved role for gp41CD in activating NF-κB to promote infection...
  39. ncbi Activation of the NF-kappaB pathway by caspase 8 and its homologs
    P M Chaudhary
    Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, Texas, TX 75390 8593, USA
    Oncogene 19:4451-60. 2000
    ..Thus, DEDs-containing caspases and caspase homolog(s) may have functions beyond their known role in the mediation of cell death. Oncogene (2000) 19, 4451 - 4460...
  40. ncbi Characterization of the Ikappa B-kinase NEMO binding domain
    Michael J May
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University Medical School, New Haven, Connecticut 06520, USA
    J Biol Chem 277:45992-6000. 2002
    ..IKK) composed of two catalytic subunits (IKKalpha and IKKbeta) and a noncatalytic regulatory component named NEMO (NF-kappaB essential modulator)...
  41. doi Solution structure of NEMO zinc finger and impact of an anhidrotic ectodermal dysplasia with immunodeficiency-related point mutation
    Florence Cordier
    Institut Pasteur, Unité de RMN des Biomolécules CNRS, URA 2185, F 75015 Paris, France
    J Mol Biol 377:1419-32. 2008
    The regulatory NEMO (NF-kappaB essential modulator) protein has a crucial role in the canonical NF-kappaB signaling pathway notably involved in immune and inflammatory responses, apoptosis and oncogenesis...
  42. doi Alterations of the IKBKG locus and diseases: an update and a report of 13 novel mutations
    Francesca Fusco
    Institute of Genetics and Biophysics Adriano Buzzati Traverso IGB CNR, Naples, Italy
    Hum Mutat 29:595-604. 2008
    ..called nuclear factor-kappaB (NF-kB) essential modulator (NEMO), gene are the most common single cause of incontinentia pigmenti (IP) in females and anhydrotic ectodermal dysplasia with immunodeficiency (EDA-ID) in males...
  43. pmc NEMO/IKKgamma regulates an early NF-kappaB-independent cell-death checkpoint during TNF signaling
    D Legarda-Addison
    Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029, USA
    Cell Death Differ 16:1279-88. 2009
    ..NF-kappaB essential modifier (NEMO)/IkappaB kinase-gamma (IKKgamma)-deficient cells are highly sensitive to apoptosis, and as NEMO is essential for NF-kappaB activation, it has ..
  44. pmc The common NF-κB essential modulator (NEMO) gene rearrangement in Korean patients with incontinentia pigmenti
    Min Jung Song
    Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
    J Korean Med Sci 25:1513-7. 2010
    b>Incontinentia pigmenti (IP) is a rare X-linked dominant disorder characterized by highly variable abnormalities of the skin, eyes and central nervous system...
  45. 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
    ..To this end, we purified and cloned a novel component common to both complexes, named IKK-associated protein 1 (IKKAP1). In vitro, IKKAP1 associated specifically with IKK2 but not IKK1...
  46. ncbi Association of the adaptor TANK with the I kappa B kinase (IKK) regulator NEMO connects IKK complexes with IKK epsilon and TBK1 kinases
    Alain Chariot
    Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892 1876, USA
    J Biol Chem 277:37029-36. 2002
    ..alpha and IKK beta subunits and a presumed regulatory protein termed NEMO (NF-kappa B essential modulator) or IKK gamma. NEMO/IKK gamma is indispensable for activation of the IKKs in response to many signals, but its mechanism of ..
  47. 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...
  48. ncbi ABIN-1 binds to NEMO/IKKgamma and co-operates with A20 in inhibiting NF-kappaB
    Claudio Mauro
    Dipartimento di Biologia e Patologia Cellulare e Molecolare, Federico II, University of Naples, Via S Pansini, 5, 80131 Naples, Italy
    J Biol Chem 281:18482-8. 2006
    ..This is composed of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit, NEMO/IKKgamma. The latter protein is essential for the activation of IKKs and NF-kappaB, but its mechanism of action is not ..
  49. ncbi Heptad repeats regulate protein phosphatase 2a recruitment to I-kappaB kinase gamma/NF-kappaB essential modulator and are targeted by human T-lymphotropic virus type 1 tax
    Sohee Hong
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA
    J Biol Chem 282:12119-26. 2007
    ..A heptad repeat in IKKgamma, helix 2 (HLX2), mediates PP2A recruitment...
  50. ncbi A case of incontinentia pigmenti in Japan and its genetic examination
    Jane Huang
    Department of Ophthalmology, School of Medicine, Fukuoka University, Fukuoka, Japan
    Jpn J Ophthalmol 51:142-5. 2007
    b>Incontinentia pigmenti (IP) is a rare X-linked dominant genodermatosis with approximately one-third of cases with associated ocular complications...
  51. pmc The RING domain and first zinc finger of TRAF6 coordinate signaling by interleukin-1, lipopolysaccharide, and RANKL
    Betty Lamothe
    Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 283:24871-80. 2008
    ..These data provide evidence for the critical role of the Ub ligase activity of TRAF6, which is coordinated via the RING domain and ZF1 to supply the necessary elements in signaling by cytokines dependent upon TRAF6...
  52. 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
    IkappaB kinase (IKK) complex is a key regulator of NF-kappaB pathways. Signal-induced interaction of the IKKgamma (NEMO) subunit with the C-terminal IKKgamma/NEMO-binding domain (gammaBD) of IKKbeta is an essential interaction for IKK ..
  53. 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...
  54. ncbi Role of adapter function in oncoprotein-mediated activation of NF-kappaB. Human T-cell leukemia virus type I Tax interacts directly with IkappaB kinase gamma
    D Y Jin
    Laboratory of Molecular Microbiology, NIAID, National Institutes of Health, Bethesda, Maryland 20892 0460, USA
    J Biol Chem 274:17402-5. 1999
    ..Thus, our findings establish IKK-gamma as a key molecule for adapting an oncoprotein-specific signaling to IKK-alpha and IKK-beta...
  55. ncbi Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKKgamma) upon receptor stimulation
    S Q Zhang
    Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel
    Immunity 12:301-11. 2000
    ..Here we show that triggering of the p55 TNF receptor induces binding of RIP to NEMO (IKKgamma), a component of the I-kappa-B-kinase (IKK) "signalosome" complex, as well as recruitment of RIP to the receptor ..
  56. ncbi Genomic rearrangement in NEMO impairs NF-kappaB activation and is a cause of incontinentia pigmenti. The International Incontinentia Pigmenti (IP) Consortium
    A Smahi
    Department of Genetics, Unité de Recherches sur les Handicaps Génétiques de l Enfant INSERMU 393, Hopital Necker Enfants Malades, Paris, France
    Nature 405:466-72. 2000
    Familial incontinentia pigmenti (IP; MIM 308310) is a genodermatosis that segregates as an X-linked dominant disorder and is usually lethal prenatally in males...
  57. ncbi An induced proximity model for NF-kappa B activation in the Nod1/RICK and RIP signaling pathways
    N Inohara
    Department of Pathology and Comprehensive Cancer Center, The University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 275:27823-31. 2000
    ..of Nod1 mediates proximity of RICK and the interaction of RICK with the gamma subunit of the IkappaB kinase (IKKgamma). Similarly, the RICK-related kinase RIP associated via its intermediate region with IKKgamma...
  58. 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
    ..of kappaB (IkappaB)-kinase (IKK) complex containing two kinases (IKKalpha and IKKbeta) and the regulatory protein NEMO (NF-kappaB essential modifier)...
  59. ncbi Activation of the Ikappa B kinases by RIP via IKKgamma /NEMO-mediated oligomerization
    J L Poyet
    Center for Apoptosis Research and the Department of Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA
    J Biol Chem 275:37966-77. 2000
    ..Substitution of the C-terminal region of IKKgamma, which interacts with RIP, with a truncated DR4 lacking its cytoplasmic death domain, produced a molecule that ..
  60. ncbi Activation of IKKalpha and IKKbeta through their fusion with HTLV-I tax protein
    G Xiao
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, Pennsylvania, PA 17033, USA
    Oncogene 19:5198-203. 2000
    ..Tax activation of IKK requires physical interaction of this viral protein with the IKK regulatory subunit, IKKgamma. The Tax/IKKgamma interaction allows Tax to engage the IKK catalytic subunits, IKKalpha and IKKbeta, although it ..
  61. ncbi Role of IKKgamma/nemo in assembly of the Ikappa B kinase complex
    X H Li
    Division of Hematology Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8594
    J Biol Chem 276:4494-500. 2001
    b>IKKgamma/NEMO is a protein that is critical for the assembly of the high molecular weight IkappaB kinase (IKK) complex...
  62. ncbi X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling
    R Doffinger
    Laboratoire de Genetique Humaine des Maladies Infectieuses, Faculte de Medecine Necker Enfants Malades, Paris, France
    Nat Genet 27:277-85. 2001
    ..IKBKG encodes NEMO, the regulatory subunit of the IKK (IkappaB kinase) complex, which is essential for NF-kappaB signaling...
  63. pmc Survival of male patients with incontinentia pigmenti carrying a lethal mutation can be explained by somatic mosaicism or Klinefelter syndrome
    S Kenwrick
    Addenbrooke s Hospital, Cambridge, UK
    Am J Hum Genet 69:1210-7. 2001
    b>Incontinentia pigmenti (IP), or "Bloch-Sulzberger syndrome," is an X-linked dominant disorder characterized by abnormalities of skin, teeth, hair, and eyes; skewed X-inactivation; and recurrent miscarriages of male fetuses...
  64. 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
    The IKK complex, containing two catalytic subunits IKKalpha and IKKbeta and a regulatory subunit NEMO, plays central roles in signal-dependent activation of NF-kappaB...
  65. ncbi Regulation of Ikappa B kinase (IKK)gamma /NEMO function by IKKbeta -mediated phosphorylation
    Shashi Prajapati
    Division of Hematology Oncology, Department of Medicine, Harold Simmons Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Biol Chem 277:24331-9. 2002
    ..kinase (IKK) complex includes the catalytic components IKKalpha and IKKbeta in addition to the scaffold protein IKKgamma/NEMO...
  66. pmc The carboxyl-terminal region of IkappaB kinase gamma (IKKgamma) is required for full IKK activation
    Constantin Makris
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, La Jolla 92093 0636, USA
    Mol Cell Biol 22:6573-81. 2002
    ..IKKgamma is encoded by an X-linked gene, deficiencies in which may result in two human genetic disorders, incontinentia pigmenti (IP) and hypohidrotic ectodermal dysplasia with severe immunodeficiency...
  67. 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
    ..Its catalytic subunits, IKKalpha and IKKbeta, require association with the regulatory IKKgamma (NEMO) component to gain full basal and inducible kinase activity...
  68. ncbi A role for NF-kappaB essential modifier/IkappaB kinase-gamma (NEMO/IKKgamma) ubiquitination in the activation of the IkappaB kinase complex by tumor necrosis factor-alpha
    Eric D Tang
    Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA
    J Biol Chem 278:37297-305. 2003
    NEMO (NF-kappaB essential modifier)/IKKgamma (IkappaB kinase-gamma) is required for the activation of the IkappaB kinase complex (IKK) by inflammatory stimuli such as tumor necrosis factor (TNF-alpha)...
  69. ncbi CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members
    Eirini Trompouki
    Institute of Immunology, Biomedical Sciences Research Center Alexander Fleming, 34 Alexander Fleming Street, Vari 16672, Greece
    Nature 424:793-6. 2003
    ..These results indicate that CYLD is a negative regulator of the cytokine-mediated activation of NF-kappaB that is required for appropriate cellular homeostasis of skin appendages...
  70. ncbi Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB
    Thijn R Brummelkamp
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Nature 424:797-801. 2003
    ..We show that CYLD binds to the NEMO (also known as IKKgamma) component of the IkappaB kinase (IKK) complex, and appears to regulate its activity through de-ubiquitination of ..
  71. 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...
  72. ncbi The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes
    Lijun Sun
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 14:289-301. 2004
    ..bind to TRAF6, induce TRAF6 oligomerization, and activate the ligase activity of TRAF6 to polyubiquitinate NEMO. These results reveal an oligomerization --> ubiquitination --> phosphorylation cascade that culminates in NF-..
  73. ncbi TAB2 and TAB3 activate the NF-kappaB pathway through binding to polyubiquitin chains
    Atsuhiro Kanayama
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Mol Cell 15:535-48. 2004
    ..These results indicate that polyubiquitin binding domains represent a new class of signaling domains that regulate protein kinase activity through a nonproteolytic mechanism...
  74. ncbi A20 is a potent inhibitor of TLR3- and Sendai virus-induced activation of NF-kappaB and ISRE and IFN-beta promoter
    Yan Yi Wang
    Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing 100871, China
    FEBS Lett 576:86-90. 2004
    ..These data suggest that A20 targets TRIF to inhibit TLR3-mediated induction of IFN-beta transcription and functions as a feedback negative regulator for TLR3 signaling and cellular anti-viral response...
  75. ncbi The Crohn's disease protein, NOD2, requires RIP2 in order to induce ubiquitinylation of a novel site on NEMO
    Derek W Abbott
    Division of Gastrointestinal Pathology, Department of Pathology, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Curr Biol 14:2217-27. 2004
    ..NOD2 can both strongly activate and negatively attenuate NF-kB signaling. The biochemical mechanism for this dual function of NOD2 is unknown...
  76. ncbi PDK1 nucleates T cell receptor-induced signaling complex for NF-kappaB activation
    Ki Young Lee
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520, USA
    Science 308:114-8. 2005
    ..activation of the IKK complex through Bcl10-MALT1-dependent ubiquitination of the IKK complex subunit known as NEMO (NF-kappaB essential modifier)...
  77. pmc Regulation of the deubiquitinating enzyme CYLD by IkappaB kinase gamma-dependent phosphorylation
    William Reiley
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Dr, Hershey, PA 17033, USA
    Mol Cell Biol 25:3886-95. 2005
    ..Interestingly, the CYLD phosphorylation requires IkappaB kinase gamma (IKKgamma) and can be induced by IKK catalytic subunits...
  78. ncbi PIDD mediates NF-kappaB activation in response to DNA damage
    Sophie Janssens
    Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Chemin des Boveresses 155, CH 1066 Epalinges, Switzerland
    Cell 123:1079-92. 2005
    ..stress, a complex between PIDD, the kinase RIP1, and a component of the NF-kappaB-activating kinase complex, NEMO, is formed...
  79. 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
    ..We show that NF-kappaB essential modulator (NEMO), the regulatory subunit of IkappaB kinase (IKK) (which phosphorylates the NF-kappaB inhibitor IkappaB), associates ..
  80. ncbi Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected]
    Chuan Jin Wu
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nat Cell Biol 8:398-406. 2006
    ..NEMO is essential for NF-kappaB activation, and NEMO dysfunction in humans is the cause of incontinentia pigmenti and hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID)...
  81. ncbi NEMO binding domain of IKK-2 encompasses amino acids 735-745
    Joann Strnad
    Drug Discovery Research, Bristol Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA
    J Mol Recognit 19:227-33. 2006
    ..Though this signalsome is comprised of IKK-1, IKK-2, and NEMO/IKKgamma, it is the interaction between IKK-2 and NEMO that is critical to formation of a functional signalsome...
  82. ncbi Activation of IKK by TNFalpha requires site-specific ubiquitination of RIP1 and polyubiquitin binding by NEMO
    Chee Kwee Ea
    Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Mol Cell 22:245-57. 2006
    ..Interestingly, polyubiquitinated RIP1 recruits IKK through the binding between the polyubiquitin chains and NEMO, a regulatory subunit of the IKK complex...
  83. ncbi The IRAK-1-BCL10-MALT1-TRAF6-TAK1 cascade mediates signaling to NF-kappaB from Toll-like receptor 4
    Wei Dong
    State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei 430072, China
    J Biol Chem 281:26029-40. 2006
    ..We show that BCL10 oligomerization is a prerequisite for BCL10 function in LPS signaling to NF-kappaB and that IRAK-1 dimerization is an important event in this process...
  84. ncbi PIASy mediates NEMO sumoylation and NF-kappaB activation in response to genotoxic stress
    Angela M Mabb
    Program in Molecular and Cellular Pharmacology, Department of Pharmacology, University of Wisconsin, Madison, WI 53706, USA
    Nat Cell Biol 8:986-93. 2006
    ..SUMO-1 modification of NEMO (NF-kappaB essential modulator), the IkappaB kinase (IKK) regulatory subunit, is critical for activation of NF-..
  85. pmc Dimerization of the I kappa B kinase-binding domain of NEMO is required for tumor necrosis factor alpha-induced NF-kappa B activity
    Ralf B Marienfeld
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University Medical School, New Haven, CT 06520, USA
    Mol Cell Biol 26:9209-19. 2006
    Previous studies have demonstrated that peptides corresponding to a six-amino-acid NEMO-binding domain from the C terminus of IkappaB kinase alpha (IKKalpha) and IKKbeta can disrupt the IKK complex and block NF-kappaB activation...
  86. 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
    ..and IKKbeta molecules in the cell are part of IKK complexes that also contain a regulatory subunit called IKKgamma or NEMO...
  87. pmc Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation
    Betty Lamothe
    Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 282:4102-12. 2007
    ..Additionally, we provide biochemical and in vivo evidence that TRAF6 serves as an E3 to directly ubiquitinate NEMO. Reconstituting TRAF6-deficent cells with various TRAF6 mutants, we clearly demonstrate the requirement for the ..
  88. ncbi Activation of NF-kappa B by the human T cell leukemia virus type I Tax oncoprotein is associated with ubiquitin-dependent relocalization of I kappa B kinase
    Nicole S Harhaj
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, Miami, Florida 33136, USA
    J Biol Chem 282:4185-92. 2007
    ..Tax activates the IkappaB kinase (IKK) via physical interaction with the regulatory subunit, IKKgamma, although it is unknown precisely how Tax activates the IKK complex...
  89. pmc Interleukin-1-induced NF-kappaB activation is NEMO-dependent but does not require IKKbeta
    Laura A Solt
    Department of Animal Biology, University of Pennsylvania School of Veterinary Medicine, PA 19104, USA
    J Biol Chem 282:8724-33. 2007
    ..kinase (IKK) complex, which contains two kinases named IKKalpha and IKKbeta and a critical regulatory subunit named NEMO. Although we have previously demonstrated that NEMO associates with both IKKs, genetic studies reveal that only its ..
  90. ncbi NEMO mutational analysis in a Japanese family with incontinentia pigmenti
    H Tada
    Eye (Lond) 21:888-90. 2007
  91. ncbi Optineurin negatively regulates TNFalpha- induced NF-kappaB activation by competing with NEMO for ubiquitinated RIP
    Guozhi Zhu
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Curr Biol 17:1438-43. 2007
    NF-kappaB essential modulator (NEMO), the regulatory subunit of the IkappaB kinase (IKK) that activates NF-kappaB, is essential for NF-kappaB activation...
  92. ncbi Ubiquitylated Tax targets and binds the IKK signalosome at the centrosome
    Y Kfoury
    Department of Internal Medicine, American University of Beirut, Beirut, Lebanon
    Oncogene 27:1665-76. 2008
    ..These observations highlight an unsuspected link between Tax-induced IKK activation and the centrosome...
  93. pmc The human T-cell leukemia virus type 1 Tax oncoprotein requires the ubiquitin-conjugating enzyme Ubc13 for NF-kappaB activation
    Noula Shembade
    Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, The University of Miami, Miller School of Medicine, 1550 NW 10 Avenue, Miami, FL 33136, USA
    J Virol 81:13735-42. 2007
    ..Finally, the interaction of Tax with NEMO is disrupted in the absence of Tax ubiquitination and Ubc13 expression, suggesting that Tax ubiquitination is ..
  94. pmc Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation
    Andrea Oeckinghaus
    GSF National Research Center for Environment and Health, Institute of Toxicology, Neuherberg, Germany
    EMBO J 26:4634-45. 2007
    ..Ubiquitin chains on Malt1 provide a docking surface for the recruitment of the IKK regulatory subunit NEMO/IKKgamma. TRAF6 associates with Malt1 in response to T-cell activation and can function as an E3 ligase for Malt1 in vitro ..
  95. ncbi Phosphorylation of serine 68 in the IkappaB kinase (IKK)-binding domain of NEMO interferes with the structure of the IKK complex and tumor necrosis factor-alpha-induced NF-kappaB activity
    Lysann Palkowitsch
    Institute of Physiological Chemistry, Ulm University, Albert Einstein Allee 11, Ulm 89081, Germany
    J Biol Chem 283:76-86. 2008
    ..Besides the two kinases IKKalpha and IKKbeta, the IKK complex contains NEMO/IKKgamma, an additional subunit with regulatory and adaptor functions...
  96. ncbi The IRAK-catalysed activation of the E3 ligase function of Pellino isoforms induces the Lys63-linked polyubiquitination of IRAK1
    Alban Ordureau
    MRC Protein Phosphorylation Unit, The Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD15 5EH, Scotland, UK
    Biochem J 409:43-52. 2008
    ..2, but not inactive mutants of these proteins, induces the formation of K63-pUb-IRAK1 and its interaction with the NEMO [NF-kappaB (nuclear factor kappaB) essential modifier] regulatory subunit of the IKK (inhibitor of NF-kappaB kinase)..
  97. pmc High-affinity interaction between IKKbeta and NEMO
    Yu Chih Lo
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    Biochemistry 47:3109-16. 2008
    The Ser/Thr-specific IkappaB kinase (IKK), which comprises IKKalpha or IKKbeta and the regulatory protein NEMO, is at the bottleneck for NF-kappaB activation. IKK activity relies on interaction between NEMO and IKKalpha or IKKbeta...
  98. pmc NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation
    Chuan Jin Wu
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 105:3023-8. 2008
    ..we show that Bcl10 undergoes K63-linked polyubiquitination in response to T cell activation and subsequently binds NEMO, the regulatory subunit of IKK. This interaction requires the ubiquitin-binding activity of NEMO...
  99. pmc Lys63-linked polyubiquitination of IRAK-1 is required for interleukin-1 receptor- and toll-like receptor-mediated NF-kappaB activation
    Dietrich B Conze
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Mol Cell Biol 28:3538-47. 2008
    ..and IRAK-1 acquired Lys63 (K63)-linked polyubiquitin chains upon IL-1 stimulation, only ubiquitinated IRAK-1 bound NEMO, the regulatory subunit of IkappaB kinase (IKK)...
  100. doi Specific recognition of linear ubiquitin chains by NEMO is important for NF-kappaB activation
    Simin Rahighi
    Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization KEK, Tsukuba, Ibaraki, Japan
    Cell 136:1098-109. 2009
    ..a key mediator of inducible transcription in immunity, requires binding of NF-kappaB essential modulator (NEMO) to ubiquitinated substrates...
  101. pmc Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains
    David Komander
    Division of Protein and Nucleic Acid Chemistry, Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK
    EMBO Rep 10:466-73. 2009
    ..We found that the UBAN (ubiquitin binding in ABIN and NEMO) motif of NEMO (NF-kappaB essential modifier) binds to linear chains exclusively, whereas the NZF (Npl4 zinc finger)..

Research Grants63

  1. MOLECULAR MECHANISMS LEADING TO RETT SYNDROME
    Uta Francke; Fiscal Year: 2002
    ..The hypothesis tat a genomic rearrangement causes two de novo mutations in Xq28 in a female with RTT and Incontinentia Pigmenti (IP), another X-linked dominant disorder lethal in males, will be tested by genomic approaches and by ..
  2. ANALYSIS AND CLONING OF A DEVELOPMENTAL SKIN LOCUS
    JEROME GORSKI; Fiscal Year: 1990
    ..research undertaken in this proposal will be directed towards the analysis of a human developmental gene, incontinentia pigmenti (IP). IP is an X-linked dominant, hemizygote lethal disorder...
  3. Molecular Analysis of Xq28-Linked Incontinentia Pigmenti
    David Nelson; Fiscal Year: 2008
    b>Incontinentia pigmenti (IP) is an X-linked dominant and male-lethal disorder that mainly affects the skin, teeth, eyes, and central nervous system...
  4. Regulation of NF-kappaB by Small Ubiquitin-Like Modifiers
    Shigeki Miyamoto; Fiscal Year: 2013
    ..We have recently uncovered a novel signaling role for SUMOylation of NEMO (NF-?B essential modulator) in NF-?B signaling...
  5. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    ..Similar to TRAF6, NF-?B essential modulator (NEMO) is subject to K63- linked ubiquitination...
  6. Validation of a Novel NF-kB Inhibitor in Inflammatory Bowel Disease
    Anthony Blikslager; Fiscal Year: 2013
    ..8K) protein transduction domain (PTD) with an I?B kinase (IKK) inhibitory sequence, "NF??B essential modulator" (NEMO) binding domain (NBD)...
  7. Negative regulation of NF-kB and inflammation by TAX1BP1
    Edward W Harhaj; Fiscal Year: 2012
    ..IKKa, but not IKKb or NEMO, is required for TNF-induced interactions among TAX1BP1, Itch, A20 and RIP1...
  8. Shen Ying Zhang; Fiscal Year: 2016
    ..Moreover, other children with mycobacterial disease and lethal HSE bear mutations in STAT1 (AR) or NEMO (X-linked recessive, XR)...
  9. Nemo-Like Kinase and the Pathogenesis of Spinal and Bulbar Muscular Atrophy
    TIFFANY WERLYNE TODD; Fiscal Year: 2013
    ..This proposal therefore investigates the role of the serine/threonine protein kinase Nemo-Like Kinase (NLK) in the pathogenesis of SBMA with the hope that NLK will prove a viable drug target in the ..
  10. NF-Kappa B regulation by Bcl10 in liver cancer
    LAKITA CAVIN; Fiscal Year: 2006
    ..abstract_text> ..
  11. Julie Horowitz; Fiscal Year: 2015
    ..I will use retroviruses to investigate if Rag activates NF[unreadable]B via ubiquitylation of NEMO. I will then investigate if non-core Rag1 regions promote NF[unreadable]B-dependent activation of the CDK2-AP1 cell ..
  12. Zhijian J Chen; Fiscal Year: 2014
    ..IKK activation requires its regulatory subunit NEMO, which contains two ubiquitin-binding domains...
  13. Derek W Abbott; Fiscal Year: 2016
    ..release through the lysine-63 (K63)-linked polyubiquitination of a novel site (K285) on the IKK scaffolding protein NEMO. We have recently extended this finding to show that the major extracellular innate immune signaling receptors, the ..
  14. JASON LEE SPERRY; Fiscal Year: 2014
    ..remaining two X-linked, TLR pathway constituents (Bruton's tyrosine kinase, BTK and NF-:B essential modulator, NEMO), for which no known functional polymorphism evidence currently exists...
  15. TRAF6 E3 LIGASE FUNCTION IN OSTEOCLASTOGENESIS
    Bryant G Darnay; Fiscal Year: 2010
    ..Endogenous TAB2 and NEMO, which are potential TRAF6 downstream signaling molecules, are also ubiquitinated upon RANK activation...
  16. Using a cyclotide-based molecular scaffold to select specific protein-protein inh
    Mark W Nowak; Fiscal Year: 2010
    ..IKK activity is modulated by an allosteric activator, NEMO. Thus, cyclotide inhibitors of the NEMO/IKK[unreadable] interaction will likely block TNFa stimulation of NF?B ..
  17. Yousef Abu-Amer; Fiscal Year: 2016
    ..The former pathway requires assembly of large IKK complex encompassing IKK1, IKK2, and IKK?, also known as NEMO. We have shown recently that interfering with the NF-?B and MAPK activation pathways, through introduction of ..
  18. TLR4 Signaling in alcoholic liver disease
    Gyongyi Szabo; Fiscal Year: 2013
    ..Kupffer cells;b) investigating the interaction between NF-kB and IRF signaling pathways using an inhibitor of IKK? (NEMO adapter) in vivo;c) evaluating the role of TNF? in maintaining an IFN?-mediated autocrine loop in the sustained ..
  19. Evaluation of NBD Peptides as an Adjunct Therapy for the Treatment of Non-Hodgkin
    PATRICK MICHAEL FLOOD; Fiscal Year: 2010
    ..has a peptide inhibitor containing an I?B kinase inhibitory sequence NF-?B essential modulator (NEMO) binding domain (NBD)...
  20. The Role of NEMO Ubiquitination in EDA-ID
    Derek W Abbott; Fiscal Year: 2012
    ..A key regulator of NF-kB signal transduction, NEMO, has recently been found to be mutated in an Immunodeficiency Disorder called called Anhidrotic (hypohydrotic) ..
  21. Yousef Abu-Amer; Fiscal Year: 2016
    ..More importantly, we discovered diminished expression of key osteoclastogenic proteins including TRAF6, NEMO and Notch-NICD. This phenomenon was associated with accumulation of NUMBL, a previously described neuron protein...
  22. Christopher A Klug; Fiscal Year: 2014
    ..Furthermore, blocking NF-?B activation in HSC by conditional deletion of the Ikk regulatory subunit, NEMO, resulted in a substantial decrease in one of the earliest multipotential progenitor subsets (c-Kit?Sca-1? cells) ..
  23. Structural and functional studies of the IkappaB kinase (IKK) complex
    Hao Wu; Fiscal Year: 2013
    ..The regulatory protein NEMO (also known as IKK? or FIP-3) interacts with IKKa and/or IKK[unreadable] to form the IKKa, IKK[unreadable] or IKKa/[..
  24. Shigeki Miyamoto; Fiscal Year: 2014
    ..This signaling pathway involves a post-translational modification (PTM) of NEMO (NF-kB essential modulator)/IKK3, the regulatory subunit of the I:B kinase (IKK) complex, by SUMO-1 (small ..
  25. Jean Laurent Casanova; Fiscal Year: 2016
    ..identified six morbid genes, including five autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1) and one X- linked (NEMO) gene...
  26. DUSANKA DANIELLE DERETIC; Fiscal Year: 2016
    ..complex, which is comprised of the small GTPases Arf4 and Rab11, the Arf GAP ASAP1, and the Arf/Rab11 effector FIP3, and determine its mode of interaction with rhodopsin at the trans-Golgi network (TGN), which is essential for ..
  27. Ari M Melnick; Fiscal Year: 2015
    ..this result and showed that Hsp90 binds and protects from degradation the BCL6 transcriptional repressor and the NEMO subunit of the IKK complex, both of which are components of oncogenic pathways in DLBCL...
  28. Michael J May; Fiscal Year: 2014
    ..and NC NF-kB activation in pro-atherogenic signaling and gene expression in EC;(3) To determine the effects of the NEMO binding domain (NBD) peptide on atherosclerosis in vivo...
  29. Regulation of NF-kB and 1kB Proteins
    Sankar Ghosh; Fiscal Year: 2010
    ..In particular we wish to understand the role of NEMO/IKKy, the regulatory subunit of the IKK complex in the activation process, Finally we will study the possible ..
  30. Jean Laurent Casanova; Fiscal Year: 2014
    ..has identified six morbid genes, including five autosomal (IFNGR1, IFNGR2, STAT1, IL12B, IL12RB1) and one X-linked (NEMO) gene...
  31. Discovery of small molecule drug candidates that disrupt the NEMO/IKK signaling c
    Stig K Hansen; Fiscal Year: 2010
    ..The protein-protein interaction between IkB Kinase (IKK) and Nf-kB Essential Modulator (NEMO), referred to as NEMO/IKK, has emerged as a promising target for inhibiting NF-kB activation: Peptides that ..
  32. A Canine Model for Human X-Linked Ectodermal Dysplasia
    Margret Casal; Fiscal Year: 2007
    ..canine equivalent to the newly described HED associated with immune deficiency in humans, caused by a defect in the NEMO gene which is also X-linked...
  33. Design of Macrocyclic Inhibitors of the NEMO/IKKa/b Protein-Protein Interaction
    Adrian Whitty; Fiscal Year: 2013
    ..The test system is the intracellular PPI target NF-?B essential modulator (NEMO), a component of the inhibitor of ?B kinase (IKK) complex...
  34. Stig K Hansen; Fiscal Year: 2014
    DESCRIPTION: Drug candidates that disrupt the NEMO/IKK signaling complex for the treatment of cancer Project Summary/Abstract Protein-protein interactions represent the largest untapped opportunity for therapeutic development, but the ..
  35. A High Throughput Protein Complementation Assay for Inhibitors of NEMO-K13 Intera
    Preet M Chaudhary; Fiscal Year: 2012
    ..We have discovered that K13, a small protein encoded by HHV8, directly interacts with the NEMO/IKK3 subunit of the IkB kinase (IKK) complex to activate the NF-kB pathway and utilizes this pathway to promote ..
  36. Lawrence P Kane; Fiscal Year: 2016
    ..activation of the classical NF-?B pathway requires complex sub-cellular regulation of the adaptor protein IKK?/NEMO. Thus, in Aim 1, we will determine the role of Zap70 and Lck in recruitment of the IKK complex to TCR microclusters...
  37. Shai Shaham; Fiscal Year: 2016
    ..We will (1) elucidate the mechanism of action of the LIT-1 NEMO-like kinase in glial compartment size control;(2) study the role of the retromer component SNX-1 in glial ..
  38. Roles of Nemo-like kinase in CaP and its effects on androgen receptor signaling
    Eva Corey; Fiscal Year: 2010
    ..We have shown that the MAPK-like protein, Nemo-like kinase (NLK) expression is altered during prostate cancer progression, and that NLK dramatically inhibits AR-..
  39. SHAWN SIAVASH JACKSON; Fiscal Year: 2014
    ..At the center of this proposal is NEMO, the NF-?B essential modulator...
  40. The role of Nemo-like kinase in neurodegeneration
    Janghoo Lim; Fiscal Year: 2012
    ..Purkinje neuron degeneration) is known, and studies to identify the underlying pathophysiology led me to uncover Nemo-like kinase (NLK) as a key protein contributing to pathogenesis...
  41. Elliott D Kieff; Fiscal Year: 2016
    ..key B-cell proteins required for LMP1 TES2 canonical NFkB activation for their role in TRAF6 and IKK activation, NEMO ubiquitination, and nuclear RelA phosphorylation...
  42. Neural ElectroMagnetic Ontologies: ERP Knowledge Representation &Integration
    DEJING DOU; Fiscal Year: 2012
    ..provided by applicant): Research in the design and implementation of "Neural ElectroMagnetic Ontologies" (NEMO) will address a critical need for tools to support representation, storage, and sharing of brain electromagnetic ..
  43. Wang Min; Fiscal Year: 2016
    ..We will determine how AIP1 via its C-terminal CC/LZ domain competes with NEMO for the RIP1 association, disrupting IKK complex formation, and how JAK2/Bmx-SOCS3 mediates AIP1 phosphorylation ..
  44. Preet M Chaudhary; Fiscal Year: 2014
    ..K13 activates the NF-kB pathway by directly interacting with the NEMO/IKK3 subunit of the IkB kinase (IKK) complex and utilizes this pathway to promote cellular survival, proliferation, ..
  45. NF-kB Inhibition of Lung Ischemia Repurfusion Injury
    Patrick Flood; Fiscal Year: 2009
    ..TheraLogics, a biotechnology company, to evaluate the effectiveness of two agents to inhibit activation of NF-(B: NEMO binding peptides that block NF-(B activation by interfering with the interaction of IKK( with IKK( and IKK(;and ..
  46. LEE MARK WETZLER; Fiscal Year: 2016
    ..vaccine candidates in a recently developed GC vaginal infection model utilizing humanized transgenic mice termed NeMo-8...
  47. WILLIAM T SULLIVAN; Fiscal Year: 2014
    ..with the recycling endosome, and its cell-cycle-regulated association with the conserved effector protein Nuf/FIP3. We hypothe- size that cell-cycle-regulated, microtubule-motor-based recruitment of Nuf/FIP3 to Rab11 at the RE ..
  48. JOANNA CHUNGYEN CHIU; Fiscal Year: 2016
    ..performed mechanistic studies on specific PER phosphorylation sites that are dependent on DOUBLETIME (DBT) and NEMO kinase activities, and found that they are integral part of a phosphorylation circuitry that sets te pace of the ..
  49. Visual Recognition Memory: Integrating Perception and Cognition
    Robert Sekuler; Fiscal Year: 2010
    ..Aim Four synthesizes NEMO, a global-matching model for item-recognition, with the Temporal Context Model (TCM)...
  50. In Vivo Function of NEMO As a Sensor of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    ..polyubiquitination of TNF receptor-associated factor 6 (TRAF6), receptor-interacting protein 1 (RIP), and the NEMO subunit of I?B kinase (IKK) plays a crucial regulatory role in immunoreceptor signaling...
  51. Functional analysis of the CYLD tumor suppressor
    JULIDE CELEBI; Fiscal Year: 2009
    ..It has been shown to interact with several members of the NF-KB signaling pathway, such as TRAF-2, TRIP, and IKKy/NEMO, and negatively regulate NF-KB activation...
  52. Alan A Aderem; Fiscal Year: 2016
    ..We have demonstrated that Sharpin acts at the level of the NEMO-containing IKK complex and controls a novel branch point in the TLR2/NF-?B pathway that is necessary for the ..
  53. Validation of a Novel NF-KB Inhibitor in Murine IBD
    Scott Plevy; Fiscal Year: 2006
    ..lysine protein transduction domain (PTD) with an IKB kinase (IKK) inhibitory sequence, "NF-KB essential modulator" (NEMO) binding domain (NBD) (collectively referred to as PTD-NBD)...
  54. SUPERSENSITIVITY ALPHA A-RECEPTORS IN HYPERTENSION
    Allan Jones; Fiscal Year: 1990
    ..The biochemical endpoints include inositol phosphate (IP, IP2, IP3), phosphatidic acid (PA), diacylglycerol (DAG) and prostaglandins (6-keto PGF1alpha, PGE2)...
  55. Blockade of NF-kappaB for Prevention/Treatment of GVHD
    Patrick Flood; Fiscal Year: 2006
    ..b>NEMO-binding peptides (NBD peptides) block the activation of NF-(B by interfering with the interaction of IKK( with IKK( ..
  56. The mechanism of NK cell defects in human NEMO deficiency
    Jordan Orange; Fiscal Year: 2009
    ..by applicant): Human primary immunodeficiency caused by hypomorphic mutation of the NF-?B essential modifier (NEMO) gene impairs several immunological functions and leads to grave infectious susceptibilities...
  57. IKK-NF-kB pathways in viral-induced lung inflammation
    Roberto Garofalo; Fiscal Year: 2004
    ..2. Characterize the effect of the NEMO-binding domain (NBD), a cell-permeable peptide that blocks IKK activity, on RSV-induced global lung gene expression ..
  58. The role of Nemo-like kinase in neurodegeneration
    Janghoo Lim; Fiscal Year: 2010
    ..Purkinje neuron degeneration) is known, and studies to identify the underlying pathophysiology led me to uncover Nemo-like kinase (NLK) as a key protein contributing to pathogenesis...
  59. GENETIC CONTROL OF SYMMETRY IN THE DROSOPHILA EYE
    Kwang Wook Choi; Fiscal Year: 1999
    ..that shows dorsal-specific white+ gene expression in the eye and two other genes involved in the rotation process, nemo and roulette...
  60. Vitamin D Promotes G1 Arrest via Cdk2 Mislocalization
    Kerry Burnstein; Fiscal Year: 2007
    ..dependent kinase 2 (Cdk2) activity and induction of cyclin dependent kinase inhibitors (CKIs), p21Cip1 and p27(ip1. We recently made the novel observation that 1,25-(OH)2D3 treatment of sensitive human prostate cancer cells ..
  61. GROWTH RELATED GENES ON CHROMOSOME 11P155
    Dale Frank; Fiscal Year: 2002
    ..In Aim 1 the applicants will isolate the mouse orthologue of the IPL gene, they will test the imprinting of murine Ip1 using interspecific mouse crosses and they will determine its intron/exon structure...
  62. Role of NEMOBP1 in LPS Stimulated Inflammatory Response
    Ato Wright; Fiscal Year: 2007
    ..a multi subunit complex composed of two catalytic subunits, IKKalpha and IKKbeta along with a regulatory subunit IKKgamma (also known as NEMO). Based on preliminary data obtained in Dr...