Ikbkg

Summary

Gene Symbol: Ikbkg
Description: inhibitor of kappaB kinase gamma
Alias: 1110037D23Rik, AI848108, AI851264, AW124339, IKK[g], NEMO, NF-kappa-B essential modulator, I-kappa-B kinase subunit gamma, IKK-gamma, IKKAP1, IKKG, NF-kappa-B essential modifier, ikB kinase subunit gamma, ikB kinase-associated protein 1, inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma, inhibitor of nuclear factor kappa-B kinase subunit gamma, mFIP-3
Species: mouse

Top Publications

  1. 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
  2. ncbi Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling
    Yaya Wang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People s Republic of China
    Nat Immunol 7:139-47. 2006
  3. 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
  4. 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
  5. 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
  6. ncbi Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation
    I M Verma
    Laboratory of Genetics, Salk Institute, San Diego, California 92186 5800, USA
    Genes Dev 9:2723-35. 1995
  7. ncbi Female mice heterozygous for IKK gamma/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti
    C Makris
    Department of Pharmacology, University of California, San Diego, La Jolla 92093, USA
    Mol Cell 5:969-79. 2000
  8. pmc Protein kinase C beta controls nuclear factor kappaB activation in B cells through selective regulation of the IkappaB kinase alpha
    Kaoru Saijo
    Laboratory of Lymphocyte Signaling, Rockefeller University, New York, NY 10021, USA
    J Exp Med 195:1647-52. 2002
  9. 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
  10. ncbi Canonical NF-kappaB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation
    Yoshiteru Sasaki
    The CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Immunity 24:729-39. 2006

Research Grants

  1. RIP2 kinase's function in Innate Immunity
    Derek Abbott; Fiscal Year: 2007

Scientific Experts

  • Fabrice Agou
  • Jesse D Riordan
  • Christian Liedtke
  • Kaoru Saijo
  • Megumi Funakoshi-Tago
  • Joseph A Fontana
  • F Mercurio
  • Xue Zhao
  • Hye Jeong Lee
  • Zhao Hui Wu
  • Lluis Espinosa
  • Marie Anne O'Donnell
  • Ali Khoshnan
  • Derek Abbott
  • T Maniatis
  • Emmanuel Derudder
  • Manolis Pasparakis
  • Tom Luedde
  • Marc Schmidt-Supprian
  • Naiara Beraza
  • Christian Trautwein
  • Shizuo Akira
  • Fuminori Tokunaga
  • Geert Van Loo
  • Tania Roskams
  • Tomoko Nakagawa
  • Kazuhiro Iwai
  • Arianna Nenci
  • Yousef Abu-Amer
  • Klaus Rajewsky
  • Vangelis Kondylis
  • Yasushi Saeki
  • Yasuhiro Yamanaka
  • Shigeki Miyamoto
  • Yann Malato
  • Muhammad Alhawagri
  • Fumiyo Ikeda
  • Ivan Dikic
  • Andy Wullaert
  • Yoshiteru Sasaki
  • Rita De Vos
  • Stuart Bloor
  • Ralph Gareus
  • Betty Lamothe
  • Dietrich B Conze
  • Alain Israel
  • Masahiro Yamamoto
  • Jiayi Yu
  • Sorina Georgiana Boaru
  • Melania Tesio
  • Chuan Jin Wu
  • Swarupa Panda
  • Dirk A Ridder
  • Hugo Leis
  • Marion Huth
  • Christopher Hooper
  • Tsuyoshi Takiuchi
  • Simon Dai
  • Anne Kathrin Müller-Rischart
  • F J Cubero
  • Siqi Liu
  • Shuo Yang
  • Flora Ngadjeua
  • H J Maier
  • Xing Liu
  • Michael Karin
  • Ralf Weiskirchen
  • Crystal M H Randall
  • Bärbel Schröfelbauer
  • Harald J Maier
  • Lingyan Wang
  • Sebastian Brähler
  • Apostolos Polykratis
  • Jeanne Chiaravalli
  • Bertrand Raynal
  • Elisabeth Fontan
  • Peter Schirmacher
  • Patrick Simon Welz
  • Ashley Wysong
  • Nikolaus Gassler
  • Yeryoung Yong
  • Mikyoung Chang
  • L Farhana
  • Yibin Yang
  • Shao Cong Sun
  • Daniel P Reay
  • Malika Al-Masaoudi
  • Shin ichi Sakata
  • Jérémie Gautheron
  • P Kratsios

Detail Information

Publications125 found, 100 shown here

  1. 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...
  2. ncbi Association of beta-arrestin and TRAF6 negatively regulates Toll-like receptor-interleukin 1 receptor signaling
    Yaya Wang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People s Republic of China
    Nat Immunol 7:139-47. 2006
    ..Thus, beta-arrestins are essential negative regulators of innate immune activation via TLR-IL-1R signaling...
  3. 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...
  4. 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...
  5. 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
    ..Tax-PP2A interaction, however, renders PP2A inactive, thus maintaining Tax-PP2A-IKK in an active state. Finally, CCR2 and LZ possibly inhibit IKK activation by stabilizing the HLX2-CCR2-LZ bundle...
  6. ncbi Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation
    I M Verma
    Laboratory of Genetics, Salk Institute, San Diego, California 92186 5800, USA
    Genes Dev 9:2723-35. 1995
  7. ncbi Female mice heterozygous for IKK gamma/NEMO deficiencies develop a dermatopathy similar to the human X-linked disorder incontinentia pigmenti
    C Makris
    Department of Pharmacology, University of California, San Diego, La Jolla 92093, USA
    Mol Cell 5:969-79. 2000
    b>IKK gamma/NEMO is the essential regulatory subunit of the I kappa B kinase (IKK), encoded by an X-linked gene in mice and humans. It is required for NF-kappa B activation and resistance to TNF-induced apoptosis...
  8. pmc Protein kinase C beta controls nuclear factor kappaB activation in B cells through selective regulation of the IkappaB kinase alpha
    Kaoru Saijo
    Laboratory of Lymphocyte Signaling, Rockefeller University, New York, NY 10021, USA
    J Exp Med 195:1647-52. 2002
    ....
  9. 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
    ..IKK has two catalytic subunits, IKKalpha and IKKbeta, and a regulatory subunit, IKKgamma or NEMO. NEMO is essential for NF-kappaB activation, and NEMO dysfunction in humans is the cause of incontinentia pigmenti ..
  10. ncbi Canonical NF-kappaB activity, dispensable for B cell development, replaces BAFF-receptor signals and promotes B cell proliferation upon activation
    Yoshiteru Sasaki
    The CBR Institute for Biomedical Research, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
    Immunity 24:729-39. 2006
    ..Inhibition of canonical NF-kappaB transcription factor activity through ablation of the essential scaffold protein NEMO arrests B cell development at the same stage as BAFF-R deficiency...
  11. 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 ..
  12. ncbi Deletion of NEMO/IKKgamma in liver parenchymal cells causes steatohepatitis and hepatocellular carcinoma
    Tom Luedde
    Institute for Genetics, University of Cologne, Zulpicher Strasse 47, 50674 Cologne, Germany
    Cancer Cell 11:119-32. 2007
    The IkappaB kinase (IKK) subunit NEMO/IKKgamma is essential for activation of the transcription factor NF-kappaB, which regulates cellular responses to inflammation. The function of NEMO in the adult liver remains elusive...
  13. ncbi Epithelial NEMO links innate immunity to chronic intestinal inflammation
    Arianna Nenci
    Institute for Genetics, University of Cologne, Zulpicher Strasse 47, 50674 Cologne, Germany
    Nature 446:557-61. 2007
    ..Intestinal epithelial-cell-specific inhibition of NF-kappaB through conditional ablation of NEMO (also called IkappaB kinase-gamma (IKKgamma)) or both IKK1 (IKKalpha) and IKK2 (IKKbeta)-IKK subunits essential for ..
  14. 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...
  15. ncbi Hepatocyte-specific IKK gamma/NEMO expression determines the degree of liver injury
    Naiara Beraza
    Medizinische Klinik III, University Hospital, RWTH Aachen, Aachen, Germany
    Gastroenterology 132:2504-17. 2007
    b>NEMO is the regulatory subunit of the I kappa B kinase (IKK) complex and is involved in controlling nuclear factor kappaB (NF-kappaB) activation. NEMO knockout mice die during embryogenesis due to massive hepatocyte apoptosis...
  16. 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)...
  17. pmc IKK1 and IKK2 cooperate to maintain bile duct integrity in the liver
    Tom Luedde
    Institute for Genetics, Centre for Molecular Medicine CMMC, and Cologne Excellence Cluster on Cellular Stress Responses in Aging associated Diseases CECAD, University of Cologne, Zulpicher Strasse 47, 50674 Cologne, Germany
    Proc Natl Acad Sci U S A 105:9733-8. 2008
    ..Unexpectedly, mice with combined ablation of IKK1 and IKK2 or IKK1 and NEMO spontaneously developed severe jaundice and fatal cholangitis characterized by inflammatory destruction of small ..
  18. doi Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation
    Fuminori Tokunaga
    Department of Biophysics and Biochemistry, Graduate School of Medicine and Cell Biology and Metabolism Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565 0871, Japan
    Nat Cell Biol 11:123-32. 2009
    ..Here, we demonstrate that LUBAC activates the canonical NF-kappaB pathway by binding to NEMO (NF-kappaB essential modulator, also called IKKgamma) and conjugates linear polyubiquitin chains onto specific Lys ..
  19. 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...
  20. pmc Hepatocyte-specific NEMO deletion promotes NK/NKT cell- and TRAIL-dependent liver damage
    Naiara Beraza
    Department of Internal Medicine III, University Hospital RWTH Aachen, Aachen 5205, Germany
    J Exp Med 206:1727-37. 2009
    ..The IKK complex mediates NF-kappaB activation and deletion of its regulatory subunit NEMO in hepatocytes (NEMO(Delta hepa)) triggers chronic inflammation and spontaneous hepatocellular carcinoma ..
  21. 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...
  22. doi Loss of caspase-8 protects mice against inflammation-related hepatocarcinogenesis but induces non-apoptotic liver injury
    Christian Liedtke
    Department of Medicine III, University Hospital, Aachen, Germany
    Gastroenterology 141:2176-87. 2011
    Disruption of the nuclear factor-κB (NF-κB) essential modulator (NEMO) in hepatocytes of mice (NEMO(Δhepa) mice) results in spontaneous liver apoptosis and chronic liver disease involving inflammation, steatosis, fibrosis, and ..
  23. 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...
  24. pmc TNFR1 determines progression of chronic liver injury in the IKKγ/Nemo genetic model
    F J Cubero
    Department of Internal Medicine III, University Hospital, RWTH Aachen, Aachen, Germany
    Cell Death Differ 20:1580-92. 2013
    ..Deletion of NF-κB essential modulator in hepatocytes (IKKγ/Nemo) causes spontaneous progression of TNF-mediated chronic hepatitis to hepatocellular carcinoma (HCC)...
  25. ncbi Complementation cloning of NEMO, a component of the IkappaB kinase complex essential for NF-kappaB activation
    S Yamaoka
    Unité de Biologie Moléculaire de l Expression Génique, URA 1773 CNRS, Institut Pasteur, Paris, France
    Cell 93:1231-40. 1998
    ..The recovered full-length cDNA encodes a 48 kDa protein, NEMO (NF-kappaB Essential MOdulator), which contains a putative leucine zipper motif...
  26. ncbi Regulation of early wave of germ cell apoptosis and spermatogenesis by deubiquitinating enzyme CYLD
    Ato Wright
    Department of Microbiology and Immunology, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033, USA
    Dev Cell 13:705-16. 2007
    ..These findings establish CYLD as a pivotal deubiquitinating enzyme (DUB) that regulates germ cell apoptosis and spermatogenesis and suggest an essential role for CYLD in controlling the RIP1/NF-kappaB signaling axis in testis...
  27. 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...
  28. pmc Severe liver degeneration and lack of NF-kappaB activation in NEMO/IKKgamma-deficient mice
    D Rudolph
    The Amgen Institute, Ontario Cancer Institute, and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada
    Genes Dev 14:854-62. 2000
    ..A novel, noncatalytic component of this kinase complex called NEMO (NF-kappaB essential modulator)/IKKgamma was identified recently...
  29. ncbi NEMO/IKK gamma-deficient mice model incontinentia pigmenti
    M Schmidt-Supprian
    Institute for Genetics, University of Cologne, Federal Republic of Germany
    Mol Cell 5:981-92. 2000
    Disruption of the X-linked gene encoding NF-kappa B essential modulator (NEMO) produces male embryonic lethality, completely blocks NF-kappa B activation by proinflammatory cytokines, and interferes with the generation and/or persistence ..
  30. pmc IkappaB kinase signaling is essential for maintenance of mature B cells
    Manolis Pasparakis
    Institute for Genetics, University of Cologne, D 50931 Cologne, Germany
    J Exp Med 196:743-52. 2002
    ..which is composed of two kinases, IKK1 and IKK2, and a regulatory subunit termed NF-kappaB essential modulator (NEMO). IKK2- and NEMO-deficient mice die at early embryonic stages...
  31. ncbi Cutting Edge: Pivotal function of Ubc13 in thymocyte TCR signaling
    Masahiro Yamamoto
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0851, Japan
    J Immunol 177:7520-4. 2006
    ..In addition, PMA/ionophore-mediated ubiquitination of NF-kappaB essential modulator (NEMO)/IkappaB kinase gamma (IKKgamma) and phosphorylation of TGF-beta-activated kinase 1 (TAK1) were nearly abolished in ..
  32. pmc TAK1-dependent signaling requires functional interaction with TAB2/TAB3
    Arnaud Besse
    Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 282:3918-28. 2007
    ..Significantly, our study provides evidence that the TAB2/TAB3 interaction with TAK1 is crucial for the activation of signaling cascades mediated by IL-1, TNF, and RANKL...
  33. pmc Impediment of NEMO oligomerization inhibits osteoclastogenesis and osteolysis
    Isra Darwech
    Department of Orthopaedic Surgery, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Cell Biochem 108:1337-45. 2009
    ..complex which contains IKKalpha, IKKbeta, and IKKgamma; the latter also known as NF-kappaB essential modulator (NEMO)...
  34. pmc Generalized immune activation as a direct result of activated CD4+ T cell killing
    Rute Marques
    Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
    J Biol 8:93. 2009
    ..In addition to progressive CD4(+) T cell immune deficiency, HIV infection is characterized by generalized immune activation, thought to arise from increased microbial exposure resulting from diminishing immunity...
  35. pmc Peptidylarginine deiminase 2 suppresses inhibitory {kappa}B kinase activity in lipopolysaccharide-stimulated RAW 264.7 macrophages
    Hye Jeong Lee
    Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 285:39655-62. 2010
    ..In vitro citrullination assay showed that incubation of purified PAD2 and IKKγ proteins in the presence of Ca(2+) citrullinated IKKγ. These results demonstrate that PAD2 interacts with IKKγ and suppresses NF-κB activity...
  36. pmc Systemic delivery of NEMO binding domain/IKKγ inhibitory peptide to young mdx mice improves dystrophic skeletal muscle histopathology
    Daniel P Reay
    Department of Neurology, University of Pittsburgh, Pittsburgh, PA 15213, USA
    Neurobiol Dis 43:598-608. 2011
    ..Peptides containing the NF-κB Essential Modulator (NEMO) binding domain (NBD) disrupt the IκB kinase complex, thus blocking NF-κB activation...
  37. pmc Lysine392, a K63-linked ubiquitination site in NEMO, mediates inflammatory osteoclastogenesis and osteolysis
    Muhammad Alhawagri
    Department of Orthopaedics, Washington University School of Medicine, St Louis, MO, USA
    J Orthop Res 30:554-60. 2012
    ..The IKK complex consists of IKKα, IKKβ, and IKKγ, also known as NEMO. NEMO has no catalytic activity and serves as a scaffold protein facilitating assembly and distal activation of NF-..
  38. pmc Cardiomyocyte-specific IκB kinase (IKK)/NF-κB activation induces reversible inflammatory cardiomyopathy and heart failure
    Harald J Maier
    Institute of Physiological Chemistry, University of Ulm, 89081 Ulm, Germany
    Proc Natl Acad Sci U S A 109:11794-9. 2012
    ..Vice versa, in cardiomyocytes lacking the regulatory subunit of IKK (IKKγ/NEMO), the induction of ISG15 was attenuated...
  39. doi Pellino3 ubiquitinates RIP2 and mediates Nod2-induced signaling and protective effects in colitis
    Shuo Yang
    Institute of Immunology, Department of Biology, National University of Ireland Maynooth, Ireland
    Nat Immunol 14:927-36. 2013
    ..Our findings identify RIP2 as a substrate for Pellino3 and Pellino3 as an important mediator in the Nod2 pathway and regulator of intestinal inflammation. ..
  40. pmc MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades
    Siqi Liu
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, United States
    elife 2:e00785. 2013
    ..These TRAF proteins promoted ubiquitination reactions that recruited NEMO to the MAVS signaling complex, leading to the activation of IKK and TBK1...
  41. pmc Two-sided ubiquitin binding of NF-κB essential modulator (NEMO) zinc finger unveiled by a mutation associated with anhidrotic ectodermal dysplasia with immunodeficiency syndrome
    Flora Ngadjeua
    From the Institut Pasteur, Unité de Biochimie Structurale et Cellulaire, Department of Structural Biology and Chemistry, CNRS, UMR 3528, 25 28 rue du Dr Roux 75724 Paris cedex 15, France
    J Biol Chem 288:33722-37. 2013
    Hypomorphic mutations in the X-linked human NEMO gene result in various forms of anhidrotic ectodermal dysplasia with immunodeficiency...
  42. doi Suppression of LUBAC-mediated linear ubiquitination by a specific interaction between LUBAC and the deubiquitinases CYLD and OTULIN
    Tsuyoshi Takiuchi
    Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Sakyo ku, Kyoto, 606 8501, Japan Department of Obstetrics and Gynecology, Graduate School of Medicine, Osaka University, Suita, Osaka, 565 0871, Japan
    Genes Cells 19:254-72. 2014
    ..Our observations provide molecular insights into the roles of ligase-deubiquitinase interactions in regulating molecular events resulting from linear ubiquitin conjugation. ..
  43. pmc Covalent modification of the NF-κB essential modulator (NEMO) by a chemical compound can regulate its ubiquitin binding properties in vitro
    Christopher Hooper
    From the McArdle Laboratory for Cancer Research, Department of Oncology, Cellular and Molecular Biology Program, University of Wisconsin Madison, Madison, Wisconsin 53705 and
    J Biol Chem 289:33161-74. 2014
    ..Ubiquitin-binding proteins play a critical role in recognizing and relaying polyubiquitin-based signaling. NEMO (NF-κB Essential Modulator) is a central player in canonical NF-κB signaling whose major function is to bind to ..
  44. pmc Regulation of T-cell activation and migration by the kinase TBK1 during neuroinflammation
    Jiayi Yu
    Department of Immunology, The University of Texas MD Anderson Cancer Center, 7455 Fannin Street, BOX 902, Houston, Texas 77030, USA
    Nat Commun 6:6074. 2015
    ..Treatment of mice with a small-molecule inhibitor of TBK1 inhibits EAE induction. These results suggest a role for TBK1 in regulating T-cell migration and establish TBK1 as a regulator of the AKT-mTORC1 signalling axis. ..
  45. doi NLRP3 inflammasome expression is driven by NF-κB in cultured hepatocytes
    Sorina Georgiana Boaru
    Institute of Molecular Pathobiochemistry, Gene Therapy and Clinical Chemistry and Pathobiochemistry, RWTH Aachen University, Aachen, Germany
    Biochem Biophys Res Commun 458:700-6. 2015
    ..In a primary murine hepatoma cells, the concomitant depletion of NEMO and Caspase-8 resulted in a significant suppression of NLRP3 expression after Lipopolysaccharide challenge...
  46. pmc Hematopoietic stem cell quiescence and function are controlled by the CYLD-TRAF2-p38MAPK pathway
    Melania Tesio
    Division of Stem Cells and Cancer, German Cancer Research Center DKFZ, 69120 Heidelberg, Germany Heidelberg Institute for Stem Cell Technology and Experimental Medicine HI STEM gGmbH, 69120 Heidelberg, Germany
    J Exp Med 212:525-38. 2015
    ..Pharmacological inhibition of p38MAPK rescued the phenotype of CYLD loss, identifying the CYLD-TRAF2-p38MAPK pathway as a novel important regulator of HSC function restricting HSC cycling and promoting dormancy. ..
  47. pmc Brain endothelial TAK1 and NEMO safeguard the neurovascular unit
    Dirk A Ridder
    Institute of Experimental and Clinical Pharmacology and Toxicology and Department of Radiation Oncology, University of Lubeck, 23562 Lübeck, Germany
    J Exp Med 212:1529-49. 2015
    Inactivating mutations of the NF-κB essential modulator (NEMO), a key component of NF-κB signaling, cause the genetic disease incontinentia pigmenti (IP)...
  48. doi Deubiquitinase MYSM1 Regulates Innate Immunity through Inactivation of TRAF3 and TRAF6 Complexes
    Swarupa Panda
    Laboratory for Molecular Infection Medicine Sweden MIMS, Umea University, 90 187, Umea, Sweden Department of Molecular Biology, Umea University, 90 187, Umea, Sweden Umeå Centre for Microbial Research UCMR, Umea University, 90 187, Umea, Sweden
    Immunity 43:647-59. 2015
    ..This study identifies MYSM1 as a key negative regulator of the innate immune system that guards against an overzealous self-destructive immune response. ..
  49. pmc NEMO Prevents Steatohepatitis and Hepatocellular Carcinoma by Inhibiting RIPK1 Kinase Activity-Mediated Hepatocyte Apoptosis
    Vangelis Kondylis
    Institute for Genetics, University of Cologne, 50674 Cologne, Germany Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases CECAD, University of Cologne, 50931 Cologne, Germany Center for Molecular Medicine CMMC, University of Cologne, 50931, Cologne, Germany
    Cancer Cell 28:582-98. 2015
    ..Mice lacking NEMO in liver parenchymal cells (LPC) spontaneously develop steatohepatitis and hepatocellular carcinoma (HCC) ..
  50. ncbi Identification of a novel tissue-specific transcriptional activator FESTA as a protein that interacts with the transcription elongation factor S-II
    Kayoko Saso
    Graduate School of Pharmaceutical Sciences, University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033
    J Biochem 133:493-500. 2003
    ..This study is the first report of a transcriptional activator that directly interacts with S-II and contains a transcriptional activation domain that cooperates with S-II via direct interaction...
  51. pmc Glycogen synthase kinase 3beta-mediated apoptosis of primary cortical astrocytes involves inhibition of nuclear factor kappaB signaling
    Joseph F Sanchez
    Program in Genetics, Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
    Mol Cell Biol 23:4649-62. 2003
    ..These findings therefore implicate GSK-3beta as a regulator of NF-kappaB activation in astrocytes and suggest that the pro-apoptotic effects of GSK-3beta may be mediated at least in part through the inhibition of NF-kappaB pathway...
  52. pmc PKC beta regulates BCR-mediated IKK activation by facilitating the interaction between TAK1 and CARMA1
    Hisaaki Shinohara
    Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230 0045, Japan
    J Exp Med 202:1423-31. 2005
    ..Hence, our data suggest that phosphorylation of CARMA1, mediated by PKCbeta, brings two key protein kinases, TAK1 and IKK, into close proximity, thereby allowing TAK1 to phosphorylate IKK...
  53. pmc Essential cytoplasmic translocation of a cytokine receptor-assembled signaling complex
    Atsushi Matsuzawa
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Science 321:663-8. 2008
    ..inhibitor of apoptosis proteins 1 and 2 (c-IAP1/2), IkappaB kinase regulatory subunit IKKgamma (also called NEMO), and mitogen-activated protein kinase (MAPK) kinase kinase MEKK1 upon ligation...
  54. doi TRAF6 negatively regulates TNFalpha-induced NF-kappaB activation
    Megumi Funakoshi-Tago
    Department of Biochemistry, Faculty of Pharmacy, Keio University, 1 5 30 Shibakoen, Minato ku, Tokyo 105 8512, Japan
    Cytokine 45:72-9. 2009
    ..Thus, these data suggest that TRAF6 negatively regulates TNFalpha-induced NF-kappaB activation through its ubiquitin ligase activity...
  55. pmc Caspase 8 inhibits programmed necrosis by processing CYLD
    Marie Anne O'Donnell
    Immunology Institute, Mount Sinai School of Medicine, New York, New York 10029, USA
    Nat Cell Biol 13:1437-42. 2011
    ..In contrast, loss of caspase 8 prevented CYLD degradation, resulting in necrotic death. A CYLD substitution mutation at Asp 215 that cannot be cleaved by caspase 8 switches cell survival to necrotic cell death in response to TNF...
  56. pmc Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice
    E G Lee
    Department of Medicine, The University of Chicago, 5841 South Maryland Avenue, MC 6084, Chicago, IL 60637, USA
    Science 289:2350-4. 2000
    ..These cells are also more susceptible than control cells to undergo TNF-mediated PCD. Thus, A20 is critical for limiting inflammation by terminating TNF-induced NF-kappaB responses in vivo...
  57. pmc TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo
    Jae Hyuck Shim
    Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Genes Dev 19:2668-81. 2005
    ..Therefore, our studies suggests that TAK1 acts as an upstream activating kinase for IKKbeta and JNK, but not IKKalpha, revealing an unexpectedly specific role of TAK1 in inflammatory signaling pathways...
  58. pmc Maximal adamantyl-substituted retinoid-related molecule-induced apoptosis requires NF-κB noncanonical and canonical pathway activation
    L Farhana
    Deparment of Medicine, John D Dingell VA Medical Center, Wayne State University, Detroit, MI, USA
    Cell Death Differ 18:164-73. 2011
    ..Cdc37 expression was required for activation of IKKα and IKKβ by 3-Cl-AHPC. These findings suggest that NF-κB pathways have an important role in 3-Cl-AHPC-mediated apoptosis...
  59. pmc The MC159 protein from the molluscum contagiosum poxvirus inhibits NF-κB activation by interacting with the IκB kinase complex
    Crystal M H Randall
    Department of Microbiology, College of Medicine, University of Illinois, Urbana, IL 61801, USA
    J Immunol 188:2371-9. 2012
    ..We propose that MC159-IKK interactions, but not MC159-TRAF2 interactions, are responsible for inhibiting NF-κB activation...
  60. pmc NEMO ensures signaling specificity of the pleiotropic IKKβ by directing its kinase activity toward IκBα
    Bärbel Schröfelbauer
    Signaling Systems Laboratory, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0375, USA
    Mol Cell 47:111-21. 2012
    ..How IKKβ enzymatic activity is targeted to stimulus-specific substrates has remained unclear. We show here that NEMO, known to be essential for IKKβ activation by inflammatory stimuli, is also a specificity factor that directs IKKβ..
  61. doi Requirement of NEMO/IKKγ for effective expansion of KRAS-induced precancerous lesions in the pancreas
    H J Maier
    Institute of Physiological Chemistry, University of Ulm, Ulm, Germany
    Oncogene 32:2690-5. 2013
    ..Pancreatic cancer development is associated with increased activity of the transcription factor NF-κB. NEMO (IKKγ) is a subunit of the IKK complex essential for the activation of canonical NF-κB signaling and has been ..
  62. doi NF-κB essential modifier is required for hepatocyte proliferation and the oval cell reaction after partial hepatectomy in mice
    Yann Malato
    Department of Internal Medicine, University Hospital RWTH, Aachen, Germany
    Gastroenterology 143:1597-1608.e11. 2012
    ..The regulatory subunit of this complex, NF-κB essential modifier (NEMO or IKBKG), is a tumor suppressor...
  63. doi Intrinsic proinflammatory signaling in podocytes contributes to podocyte damage and prolonged proteinuria
    Sebastian Brähler
    Univ of Cologne, Dept II of Internal Medicine, Cologne, Germany
    Am J Physiol Renal Physiol 303:F1473-85. 2012
    ..Here, we inhibited NF-κB signaling in podocytes by specific ablation of the NF-κB essential modulator (NEMO, IKKγ)...
  64. doi The E3 ligase parkin maintains mitochondrial integrity by increasing linear ubiquitination of NEMO
    Anne Kathrin Müller-Rischart
    Neurobiochemistry, Adolf Butenandt Institute, Ludwig Maximilians University, 80336 Munich, Germany
    Mol Cell 49:908-21. 2013
    ..to the linear ubiquitin assembly complex and increases linear ubiquitination of NF-κB essential modulator (NEMO), which is essential for canonical NF-κB signaling...
  65. pmc Negative regulation of TLR inflammatory signaling by the SUMO-deconjugating enzyme SENP6
    Xing Liu
    State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
    PLoS Pathog 9:e1003480. 2013
    ..ubiquitin-like modifier 2/3 (SUMO-2/3) is conjugated onto the Lysine residue 277 of NF-κB essential modifier (NEMO/IKKγ), and this impairs the deubiquitinase CYLD to bind NEMO, thus strengthening the inhibitor of κB kinase (IKK) ..
  66. 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...
  67. pmc CIKS, a connection to Ikappa B kinase and stress-activated protein kinase
    A Leonardi
    Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1876, USA
    Proc Natl Acad Sci U S A 97:10494-9. 2000
    ..IKKalpha and IKKbeta are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-kappaB essential modulator)/IKKgamma...
  68. 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
    ..IKK) complex includes the catalytic components IKKalpha and IKKbeta in addition to the scaffold protein IKKgamma/NEMO. Increases in the activity of the IKK complex result in the phosphorylation and subsequent degradation of IkappaB ..
  69. ncbi BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells
    Estefania Claudio
    Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1876, USA
    Nat Immunol 3:958-65. 2002
    ..B kinase (IKK) complex, predominantly by the IKK beta catalytic subunit, and requires the regulatory subunit IKK gamma (NEMO)...
  70. ncbi The trimerization domain of NEMO is composed of the interacting C-terminal CC2 and LZ coiled-coil subdomains
    Fabrice Agou
    Unité de Régulation Enzymatique des Activités Cellulaires, CNRS URA 2185, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France
    J Biol Chem 279:27861-9. 2004
    b>NEMO (NF-kappaB essential modulator) plays a key role in the canonical NF-kappaB pathway as the scaffold/regulatory component of the IkappaB kinase (IKK) complex...
  71. ncbi The IkappaB kinase (IKK) inhibitor, NEMO-binding domain peptide, blocks osteoclastogenesis and bone erosion in inflammatory arthritis
    Simon Dai
    Department of Orthopaedics and Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 279:37219-22. 2004
    ..The IKK complex contains primarily IKKalpha, IKKbeta, and the regulatory kinase IKKgamma, also known as NEMO. NEMO regulates the IKK complex activity through its binding to carboxyl-terminal region of IKKalpha and IKKbeta, ..
  72. ncbi Activation of the IkappaB kinase complex and nuclear factor-kappaB contributes to mutant huntingtin neurotoxicity
    Ali Khoshnan
    Biology Division, California Institute of Technology, Pasadena, California 91125, USA
    J Neurosci 24:7999-8008. 2004
    ..Therefore, aberrant NF-kappaB activation may contribute to the neurodegeneration induced by mutant Htt...
  73. ncbi IKKgamma inhibits activation of NF-kappaB by NIK
    Woo Jong Kwon
    Department of Microbiology, College of Natural Sciences, Changwon National University, Changwon 641 773, Korea
    Mol Cells 18:200-6. 2004
    ..Our results suggest that overexpression of IKKgamma inhibits activation of NF-kappaB by NIK by competing with NIK for interaction with IKKbeta...
  74. ncbi Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing
    Shin Maeda
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0723, USA
    Science 307:734-8. 2005
    ..These effects are linked to increased susceptibility to bacterial-induced intestinal inflammation and identify NOD2 as a positive regulator of NF-kappaB activation and IL-1beta secretion...
  75. ncbi Ectoderm-targeted overexpression of the glucocorticoid receptor induces hypohidrotic ectodermal dysplasia
    Jose Luis Cascallana
    Department of Animal Pathology, Veterinary Faculty, University of Santiago de Compostela, E 27002 Lugo, Spain
    Endocrinology 146:2629-38. 2005
    ....
  76. ncbi Oxidative stress transiently decreases the IKK complex (IKKalpha, beta, and gamma), an upstream component of NF-kappaB signaling, after transient focal cerebral ischemia in mice
    Yun S Song
    Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA
    J Cereb Blood Flow Metab 25:1301-11. 2005
    ..These results suggest that ROS are implicated in transient downregulation of IKKalpha, beta, and gamma in cerebral ischemia...
  77. ncbi Skin lesion development in a mouse model of incontinentia pigmenti is triggered by NEMO deficiency in epidermal keratinocytes and requires TNF signaling
    Arianna Nenci
    Mouse Biology Unit, European Molecular Biology Laboratory, Via Ramarini 32, 00016 Monterotondo Scalo, Rome, Italy
    Hum Mol Genet 15:531-42. 2006
    NF-kappaB essential modulator (NEMO), the regulatory subunit of the IkappaB kinase, is essential for NF-kappaB activation...
  78. ncbi IkappaB kinase-alpha is critical for interferon-alpha production induced by Toll-like receptors 7 and 9
    Katsuaki Hoshino
    Laboratory for Host Defense, RIKEN Research Center for Allergy and Immunology, Suehiro cho 1 7 22, Tsurumi ku, Yokohama, Kanagawa 230 0045, Japan
    Nature 440:949-53. 2006
    ..Furthermore, IKK-alpha associated with and phosphorylated IRF-7. Our results identify a role for IKK-alpha in TLR7/9 signalling, and highlight IKK-alpha as a potential target for manipulating TLR-induced IFN-alpha production...
  79. ncbi TLR8-mediated NF-kappaB and JNK activation are TAK1-independent and MEKK3-dependent
    Jinzhong Qin
    Department of Immunology, Cleveland Clinic Foundation, Ohio 44195, USA
    J Biol Chem 281:21013-21. 2006
    ..We postulate that TLR8-mediated MEKK3-dependent IKKgamma phosphorylation might play an important role in the activation of IKK complex, leading to IkappaBalpha phosphorylation...
  80. ncbi Endothelial nitric oxide synthase (NOS3) knockout decreases NOS2 induction, limiting hyperoxygenation and conferring protection in the postischemic heart
    Xue Zhao
    Davis Heart and Lung Research Institute and the Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH, USA
    Am J Physiol Heart Circ Physiol 292:H1541-50. 2007
    ....
  81. pmc Coordinated regulation of Toll-like receptor and NOD2 signaling by K63-linked polyubiquitin chains
    Derek W Abbott
    Department of Pathology, Case Western Reserve University School of Medicine, Room 5123 Wolstein Research Building, Cleveland, OH 44106, and Department of Pathology, Brigham and Women s Hospital, Boston, MA, USA
    Mol Cell Biol 27:6012-25. 2007
    ..2), regulates the formation of K63-linked polyubiquitin chains on the I kappa kinase (IKK) scaffolding protein, NEMO (NF-kappaB essential modifier)...
  82. doi Nanog maintains pluripotency of mouse embryonic stem cells by inhibiting NFkappaB and cooperating with Stat3
    Josema Torres
    Wellcome Trust Centre for Stem Cell Research, Tennis Court Road, Cambridge CB2 1QR, UK
    Nat Cell Biol 10:194-201. 2008
    ..proteins promoted differentiation, whereas inhibition of NFkappaB signalling, either by genetic ablation of the Ikbkg gene or overexpression of the IkappaBalpha super-repressor, increased expression of pluripotency markers...
  83. doi Genetic components of the circadian clock regulate thrombogenesis in vivo
    Elizabeth J Westgate
    Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, USA
    Circulation 117:2087-95. 2008
    ..Although genes relevant to hemostasis and vascular integrity undergo circadian oscillation, the role of the molecular clock in thrombotic events remains to be established...
  84. pmc Preliminary ocular histopathological observations on heterozygous NEMO-deficient mice
    Stephen F Oster
    Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, MD 21287 9115, USA
    Exp Eye Res 88:613-6. 2009
    ..of patients with incontinentia pigmenti (IP) have a mutation in the nuclear factor-kappa-beta essential modulator (NEMO) gene, and mice with a targeted deletion of NEMO exhibit skin pathology remarkably similar to the human disease...
  85. ncbi [Influence of inhibitory KappaB protein kinase alpha and gamma genes silencing induced by RNA interference on nuclear factor-KappaB signal pathway]
    Hai long Chen
    Department of Surgery, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning, China
    Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 21:131-4. 2009
    ....
  86. pmc Development of immunoglobulin lambda-chain-positive B cells, but not editing of immunoglobulin kappa-chain, depends on NF-kappaB signals
    Emmanuel Derudder
    Immune Disease Institute, Boston, Massachusetts, USA
    Nat Immunol 10:647-54. 2009
    ..This second phase of development is dependent on NF-kappaB signals, which can be substituted by transgenic expression of the prosurvival factor Bcl-2...
  87. pmc Inhibition of osteoblastic bone formation by nuclear factor-kappaB
    Jia Chang
    Division of Oral Biology and Medicine, Laboratory of Molecular Signaling, School of Dentistry and Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, California, USA
    Nat Med 15:682-9. 2009
    ..Taken together, our results suggest that targeting IKK-NF-kappaB may help to promote bone formation in the treatment of osteoporosis and other bone diseases...
  88. doi Crystal structure of the NEMO ubiquitin-binding domain in complex with Lys 63-linked di-ubiquitin
    Azusa Yoshikawa
    Structural Biology Laboratory, Life Science Division, Synchrotron Radiation Research Organization and Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113 0032, Japan
    FEBS Lett 583:3317-22. 2009
    b>NEMO is essential for activation of the NF-kappaB signaling pathway, which is regulated by ubiquitination of proteins...
  89. doi Antioxidant amelioration of dilated cardiomyopathy caused by conditional deletion of NEMO/IKKgamma in cardiomyocytes
    P Kratsios
    European Molecular Biology Laboratory, Mouse Biology Unit, Campus A Buzzati Traverso, Rome, Italy
    Circ Res 106:133-44. 2010
    ..Insight into the function of nuclear factor (NF)-kappaB in the adult heart has been hampered by the embryonic lethality of constitutive NF-kappaB inactivation...
  90. doi DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling between dimerization and ubiquitin binding
    Olivera Grubisha
    Unité de Biochimie Structurale et Cellulaire, Institut Pasteur, CNRS, URA 2185, Paris, France
    J Mol Biol 395:89-104. 2010
    b>NEMO is an integral part of the IkappaB kinase complex and serves as a molecular switch by which the NF-kappaB signaling pathway can be regulated...
  91. doi A nuclear poly(ADP-ribose)-dependent signalosome confers DNA damage-induced IkappaB kinase activation
    Michael Stilmann
    Max Delbruck Center for Molecular Medicine, Robert Rossle Strasse 10, 13125 Berlin, Germany
    Mol Cell 36:365-78. 2009
    ..kinase ataxia talengiectasia mutated (ATM) have been implicated to SUMOylate and phosphorylate nuclear IKKgamma (NEMO) in a consecutive mode of action, which in turn results in activation of cytoplasmic IKK holocomplexes...
  92. pmc Expression of an IKKgamma splice variant determines IRF3 and canonical NF-kappaB pathway utilization in ssRNA virus infection
    Ping Liu
    Department of Medicine, University of Texas Medical Branch UTMB, Galveston, Texas, United States of America
    PLoS ONE 4:e8079. 2009
    ..MAVS to activate divergent rate-limiting kinases downstream controlling the NF-kappaB and IRF3 pathways. Previously we discovered a ubiquitous IKKgamma splice-variant, IKKgammaDelta, that exhibits distinct signaling properties...
  93. pmc IKK{gamma} protein is a target of BAG3 regulatory activity in human tumor growth
    Massimo Ammirante
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, La Jolla, CA 92093 0723, USA
    Proc Natl Acad Sci U S A 107:7497-502. 2010
    ..As a proof of principle, we show that treatment of a mouse xenograft tumor model with bag3siRNA-adenovirus that down-regulates bag3 results in reduced tumor growth and increased animal survival...
  94. doi TAK1 suppresses a NEMO-dependent but NF-kappaB-independent pathway to liver cancer
    Kira Bettermann
    Department of Internal Medicine III, University Hospital RWTH Aachen, D 52074 Aachen, Germany
    Cancer Cell 17:481-96. 2010
    ..depends on NF-kappaB-independent functions of the I kappaB-kinase (IKK)-subunit NF-kappaB essential modulator (NEMO)...
  95. doi Identification of a new NEMO/TRAF6 interface affected in incontinentia pigmenti pathology
    Jérémie Gautheron
    INSERM U781, Hôpital Necker Enfants Malades and Université Paris Descartes, 75015 Paris, France
    Hum Mol Genet 19:3138-49. 2010
    NF-kappaB Essential MOdulator (NEMO) has been shown to play a critical role in NF-kappaB activation, as the regulatory subunit of IkappaB kinase...
  96. doi Telomere-independent Rap1 is an IKK adaptor and regulates NF-kappaB-dependent gene expression
    Hsiangling Teo
    Laboratory of NFkappaB Signaling, Proteos, Singapore 138673, Singapore
    Nat Cell Biol 12:758-67. 2010
    ..These results identify the first cytoplasmic role of Rap1 and provide a mechanism through which it regulates an important signalling cascade in mammals, independent of its ability to regulate telomere function...
  97. pmc IKK and NF-kappaB-mediated regulation of Claspin impacts on ATR checkpoint function
    Niall Steven Kenneth
    Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dundee, Scotland, UK
    EMBO J 29:2966-78. 2010
    ..These results uncover a novel function for IKK and NF-kappaB modulating the DNA-damage checkpoint response, allowing the cell to integrate different signalling pathways with the DNA-damage response...
  98. pmc The Notch/Hes1 pathway sustains NF-κB activation through CYLD repression in T cell leukemia
    Lluis Espinosa
    Cancer Research Program, Institut Municipal d Investigacions Mediques, IMIM, Hospital del Mar, 08003 Barcelona, Spain
    Cancer Cell 18:268-81. 2010
    ....
  99. pmc ATM- and NEMO-dependent ELKS ubiquitination coordinates TAK1-mediated IKK activation in response to genotoxic stress
    Zhao Hui Wu
    Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA
    Mol Cell 40:75-86. 2010
    ..Here we show that ATM activates the IKK kinase TAK1 in a manner dependent on IKKγ/NEMO and ELKS (a protein rich in glutamate, leucine, lysine, and serine)...
  100. pmc NF-κB inhibition protects against tumor-induced cardiac atrophy in vivo
    Ashley Wysong
    Duke University School of Medicine, Durham, North Carolina, USA
    Am J Pathol 178:1059-68. 2011
    ..two novel drugs designed to specifically inhibit NF-κB by targeting the IκB kinase (IKK) complex: Compound A and NEMO binding domain (NBD) peptide...

Research Grants1

  1. RIP2 kinase's function in Innate Immunity
    Derek Abbott; Fiscal Year: 2007
    ..This grant application aims to define the preferred peptide phosphorylation sites of RIP2, to map the phosphorylation site of TRAF6 and to identify the physiologic significance of RIP2's phosphorylation of TRAF6. ..