tnf receptor associated factor 6

Summary

Summary: A signal transducing tumor necrosis factor receptor associated factor that is involved in regulation of NF-KAPPA B signalling and activation of JNK MITOGEN-ACTIVATED PROTEIN KINASES.

Top Publications

  1. 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
  2. ncbi IRAK-M is a negative regulator of Toll-like receptor signaling
    Koichi Kobayashi
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell 110:191-202. 2002
  3. 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
  4. 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
  5. pmc TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling
    M A Lomaga
    Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 2S2
    Genes Dev 13:1015-24. 1999
  6. ncbi T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma
    H Takayanagi
    Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo, Japan
    Nature 408:600-5. 2000
  7. ncbi ASK1 is essential for JNK/SAPK activation by TRAF2
    H Nishitoh
    Department of Biochemistry, Cancer Institute, Tokyo, Japan
    Mol Cell 2:389-95. 1998
  8. ncbi Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors
    Akinori Takaoka
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Nature 434:243-9. 2005
  9. ncbi Distinct molecular mechanism for initiating TRAF6 signalling
    Hong Ye
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    Nature 418:443-7. 2002
  10. ncbi CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: regulation of CD40 signaling through multiple TRAF binding sites and TRAF hetero-oligomerization
    S S Pullen
    Department of Biology, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut 06877 0368, USA
    Biochemistry 37:11836-45. 1998

Detail Information

Publications206 found, 100 shown here

  1. 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...
  2. ncbi IRAK-M is a negative regulator of Toll-like receptor signaling
    Koichi Kobayashi
    Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA
    Cell 110:191-202. 2002
    ..Endotoxin tolerance, a protection mechanism against endotoxin shock, was significantly reduced in IRAK-M(-/-) cells. Thus, IRAK-M regulates TLR signaling and innate immune homeostasis...
  3. 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...
  4. 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
    ..These results reveal an oligomerization --> ubiquitination --> phosphorylation cascade that culminates in NF-kappaB activation in T lymphocytes...
  5. pmc TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling
    M A Lomaga
    Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada M5S 2S2
    Genes Dev 13:1015-24. 1999
    ..These findings establish unexpectedly diverse and critical roles for TRAF6 in perinatal and postnatal survival, bone metabolism, LPS, and cytokine signaling...
  6. ncbi T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-gamma
    H Takayanagi
    Department of Immunology, Faculty of Medicine and Graduate School of Medicine, University of Tokyo, Japan
    Nature 408:600-5. 2000
    ..Our results may offer a therapeutic approach to treat the inflammation-induced tissue breakdown...
  7. ncbi ASK1 is essential for JNK/SAPK activation by TRAF2
    H Nishitoh
    Department of Biochemistry, Cancer Institute, Tokyo, Japan
    Mol Cell 2:389-95. 1998
    ..In untransfected mammalian cells, ASK1 rapidly associates with TRAF2 in a TNF-dependent manner. Thus, ASK1 is a mediator of TRAF2-induced JNK activation...
  8. ncbi Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors
    Akinori Takaoka
    Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Tokyo 113 0033, Japan
    Nature 434:243-9. 2005
    ..Thus, our study identifies IRF-5 as a new, principal downstream regulator of the TLR-MyD88 signalling pathway and a potential target of therapeutic intervention to control harmful immune responses...
  9. ncbi Distinct molecular mechanism for initiating TRAF6 signalling
    Hong Ye
    Department of Biochemistry, Weill Medical College of Cornell University, New York, New York 10021, USA
    Nature 418:443-7. 2002
    ..Our studies identify a universal mechanism by which TRAF6 regulates several signalling cascades in adaptive immunity, innate immunity and bone homeostasis...
  10. ncbi CD40-tumor necrosis factor receptor-associated factor (TRAF) interactions: regulation of CD40 signaling through multiple TRAF binding sites and TRAF hetero-oligomerization
    S S Pullen
    Department of Biology, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Connecticut 06877 0368, USA
    Biochemistry 37:11836-45. 1998
    ..Relative affinities and competition of individual and hetero-oligomeric TRAF proteins for CD40 binding sites may contribute to receptor specificity and cell-type selectivity in CD40-dependent signaling...
  11. ncbi TRAF6 is a signal transducer for interleukin-1
    Z Cao
    Tularik Inc, South San Francisco, California 94080, USA
    Nature 383:443-6. 1996
    ..These findings indicate that TRAF proteins may function as signal transducers for distinct receptor families and that TRAF6 participates in IL-1 signalling...
  12. ncbi TLR signaling pathways
    Kiyoshi Takeda
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, and ERATO, Japan Science and Technology Corporation, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Semin Immunol 16:3-9. 2004
    ..Thus, TIR domain-containing adaptors provide specificity of TLR signaling...
  13. ncbi Tumor necrosis factor receptor-associated factors (TRAFs)
    J R Bradley
    Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke s Hospital, Hills Road, Cambridge CB2 2QQ, UK
    Oncogene 20:6482-91. 2001
    ..TRAF proteins are expressed in normal and diseased tissue in a regulated fashion, suggesting that they play an important role in physiological and pathological processes...
  14. ncbi All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction
    Jee Y Chung
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    J Cell Sci 115:679-88. 2002
    ..We raise additional questions and propose hypotheses regarding the molecular basis of TRAF signaling specificity...
  15. ncbi The tumor suppressor cylindromatosis (CYLD) acts as a negative regulator for toll-like receptor 2 signaling via negative cross-talk with TRAF6 AND TRAF7
    Hiroki Yoshida
    Gonda Department of Cell and Molecular Biology, House Ear Institute, University of Southern California, Los Angeles, California 90057, USA
    J Biol Chem 280:41111-21. 2005
    ..These findings provide novel insights into autoregulation and negative regulation of TLR signaling...
  16. ncbi TRANCE, a TNF family member, activates Akt/PKB through a signaling complex involving TRAF6 and c-Src
    B R Wong
    Laboratory of Immunology, Rockefeller University, New York, New York 10021, USA
    Mol Cell 4:1041-9. 1999
    ..These results define a mechanism by which TRANCE activates Src family kinases and PKB and provide evidence of cross-talk between TRAF proteins and Src family kinases...
  17. 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
    ..These findings suggest a biochemical mechanism for the faulty cytokine balance seen in Crohn's disease...
  18. pmc Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20
    Emre E Turer
    Gastrointestinal Division, Department of Medicine, Biomedical Sciences Program, University of California, San Francisco, San Francisco, CA 94143, USA
    J Exp Med 205:451-64. 2008
    ..These findings provide novel insights into how physiological TLR signals are regulated...
  19. ncbi Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts
    Hiroshi Takayanagi
    Department of Immunology, University of Tokyo, Hongo 7 3 1, Bunkyo ku, Japan
    Dev Cell 3:889-901. 2002
    ..Thus, NFATc1 may represent a master switch for regulating terminal differentiation of osteoclasts, functioning downstream of RANKL...
  20. ncbi A RANK/TRAF6-dependent signal transduction pathway is essential for osteoclast cytoskeletal organization and resorptive function
    Allison P Armstrong
    Department of Molecular Biology, Immunex Corporation, Seattle, Washington 98101, USA
    J Biol Chem 277:44347-56. 2002
    ..These studies are the first to define the functional domains of the RANK cytoplasmic tail that control specific differentiation and activation pathways in osteoclasts...
  21. pmc Interleukin-1 (IL-1) induces the Lys63-linked polyubiquitination of IL-1 receptor-associated kinase 1 to facilitate NEMO binding and the activation of IkappaBalpha kinase
    Mark Windheim
    MRC Protein Phosphorylation Unit, College of Life Sciences, The Sir James Black Centre, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    Mol Cell Biol 28:1783-91. 2008
    ..Our data suggest a model in which the recruitment of the NEMO-IKK complex to K63-pUb-IRAK1 and the recruitment of the TAK1 complex to TRAF6 facilitate the TAK1-catalyzed activation of IKK by the TRAF6-IRAK1 complex...
  22. ncbi Dependence of self-tolerance on TRAF6-directed development of thymic stroma
    Taishin Akiyama
    Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Science 308:248-51. 2005
    ..Engraftment of thymic stroma of TRAF6(-/-) embryos into athymic nude mice induced autoimmunity. Thus, TRAF6 directs the development of thymic stroma and represents a critical point of regulation for self-tolerance and autoimmunity...
  23. ncbi Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif
    B G Darnay
    Cytokine Research Laboratory, Department of Molecular Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 274:7724-31. 1999
    ....
  24. ncbi The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses
    David L Boone
    Department of Medicine, University of California at San Francisco, San Francisco, California 94143 0451, USA
    Nat Immunol 5:1052-60. 2004
    ..The critical function of this deubiquitinating enzyme in the restriction of TLR signals emphasizes the importance of the regulation of ubiquitin conjugation in innate immune cells...
  25. pmc TRAF6 autoubiquitination-independent activation of the NFkappaB and MAPK pathways in response to IL-1 and RANKL
    Matthew C Walsh
    Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA
    PLoS ONE 3:e4064. 2008
    ..Collectively, our results suggest that while TRAF6 autoubiquitination may serve as a marker of activation, it is unlikely to underpin RING finger-dependent TRAF6 function...
  26. ncbi The type I TGF-beta receptor engages TRAF6 to activate TAK1 in a receptor kinase-independent manner
    Alessandro Sorrentino
    Ludwig Institute for Cancer Research, Rudbeck Laboratory, Uppsala University, Sweden, Dag Hammarskjoldsv 20, SE 75185 Uppsala, Sweden
    Nat Cell Biol 10:1199-207. 2008
    ..Our data show that TGF-beta specifically activates TAK1 through interaction of TbetaRI with TRAF6, whereas activation of Smad2 is not dependent on TRAF6...
  27. pmc TRAF6 mediates Smad-independent activation of JNK and p38 by TGF-beta
    Motozo Yamashita
    Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA
    Mol Cell 31:918-24. 2008
    ..Our results indicate that TGF-beta activates JNK and p38 through a mechanism similar to that operating in the interleukin-1beta/Toll-like receptor pathway...
  28. pmc Deficient CD40-TRAF6 signaling in leukocytes prevents atherosclerosis by skewing the immune response toward an antiinflammatory profile
    Esther Lutgens
    Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht 6200 MD, Netherlands
    J Exp Med 207:391-404. 2010
    ....
  29. ncbi Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes
    T Kawai
    Department of Host Defense, Research Institute for Microbial Diseases, Japan Science and Technology Corporation, Osaka University, Osaka, Japan
    J Immunol 167:5887-94. 2001
    ....
  30. ncbi Signal integration and diversification through the p62 scaffold protein
    Jorge Moscat
    Department of Genome Science, Genome Research Institute, University of Cincinnati, 2180 E Galbraith Road, Cincinnati, OH 45237, USA
    Trends Biochem Sci 32:95-100. 2007
    ..The availability of mice in which p62 has been genetically inactivated is providing new insight into the mechanism and function of p62 at a whole-organism level...
  31. ncbi The CD40-TRAF6 axis is the key regulator of the CD40/CD40L system in neointima formation and arterial remodeling
    Marjo M P C Donners
    Department of Pathology, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands
    Blood 111:4596-604. 2008
    ..This identifies the CD40-TRAF6 axis as a potential therapeutic target in vascular disease...
  32. ncbi The RNA helicase Lgp2 inhibits TLR-independent sensing of viral replication by retinoic acid-inducible gene-I
    Simon Rothenfusser
    Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA 01605, USA
    J Immunol 175:5260-8. 2005
    ..We propose that Lgp2 acts as a negative feedback regulator of antiviral signaling by sequestering dsRNA from RIG-I...
  33. ncbi TRAF6 is a critical factor for dendritic cell maturation and development
    Takashi Kobayashi
    Abramson Family Cancer Research Institute, Philadelphia, PA 19104, USA
    Immunity 19:353-63. 2003
    ..Together these results indicate that TRAF6 regulates the critical processes required for maturation, activation, and development of DCs, the primary cellular bridge between innate and adaptive immunity...
  34. pmc Ubiquitin signalling in the NF-kappaB pathway
    Zhijian J Chen
    Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9148, USA
    Nat Cell Biol 7:758-65. 2005
    ..Recent studies have revealed several enzymes involved in the ubiquitination and deubiquitination of signalling proteins that mediate IKK activation through a degradation-independent mechanism...
  35. ncbi Involvement of TNF receptor-associated factor 6 in IL-25 receptor signaling
    Yuko Maezawa
    Department of Allergy and Clinical Immunology, Graduate School of Medicine, Chiba University, Chiba, Japan
    J Immunol 176:1013-8. 2006
    ..Taken together, these results indicate that TRAF6 plays a critical role in IL-25R-mediated NF-kappaB activation and gene expression...
  36. ncbi Severe osteopetrosis, defective interleukin-1 signalling and lymph node organogenesis in TRAF6-deficient mice
    A Naito
    Department of Oncology, The Institute of Medical Science, The University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Genes Cells 4:353-62. 1999
    ..However, the functions of TRAF6 in vivo remain unidentified...
  37. pmc Strength of TRAF6 signalling determines osteoclastogenesis
    Yuho Kadono
    Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, 308 BRB II III, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104, USA
    EMBO Rep 6:171-6. 2005
    ..Our results suggest that differences in the osteoclastogenesis-inducing capacity of TRANCE-R versus other TRAF6-associated receptors may in part stem from a quantitative difference in the TRAF6-mediated signals...
  38. ncbi Lysine 63 polyubiquitination of the nerve growth factor receptor TrkA directs internalization and signaling
    Thangiah Geetha
    Department of Biological Sciences, Program in Cellular and Molecular Biosciences, Auburn University, Auburn, Alabama 36849, USA
    Mol Cell 20:301-12. 2005
    ..These findings reveal that polyubiquitination serves as a common platform for the control of receptor internalization and signaling...
  39. ncbi IRAK (Pelle) family member IRAK-2 and MyD88 as proximal mediators of IL-1 signaling
    M Muzio
    University of Michigan Medical School, Department of Pathology, Ann Arbor, MI 48109, USA
    Science 278:1612-5. 1997
    ..Dominant negative forms of either attenuate IL-1R-mediated NF-kappaB activation. Therefore, IRAK-2 and MyD88 may provide additional therapeutic targets for inhibiting IL-1-induced inflammation...
  40. ncbi Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6
    Hans Hacker
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Nature 439:204-7. 2006
    ....
  41. pmc IRAK-4: a novel member of the IRAK family with the properties of an IRAK-kinase
    Shyun Li
    Tularik, Inc, 2 Corporate Drive, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 99:5567-72. 2002
    ....
  42. ncbi Mediation of TNF receptor-associated factor effector functions by apoptosis signal-regulating kinase-1 (ASK1)
    K P Hoeflich
    Department of Medical Biophysics, Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada
    Oncogene 18:5814-20. 1999
    ..Hence, ASK1 is a common mediator of TRAF-regulated SAPK and apoptosis signaling, and the TRAF2 - ASK1 connection completes the signaling cascade from TNF to SAPK/JNK activation...
  43. ncbi TAB2, a novel adaptor protein, mediates activation of TAK1 MAPKKK by linking TAK1 to TRAF6 in the IL-1 signal transduction pathway
    G Takaesu
    Department of Molecular Biology, Graduate School of Science, Nagoya University and CREST, Japan
    Mol Cell 5:649-58. 2000
    ..These results define TAB2 as an adaptor linking TAK1 and TRAF6 and as a mediator of TAK1 activation in the IL-1 signaling pathway...
  44. pmc TRAF6-dependent mitogen-activated protein kinase activation differentially regulates the production of interleukin-12 by macrophages in response to Toxoplasma gondii
    Nicola J Mason
    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Infect Immun 72:5662-7. 2004
    ..The studies presented here demonstrate for the first time that the production of IL-12(p40) in response to toxoplasma is dependent upon TRAF6 and p38 MAPK...
  45. 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...
  46. 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
    ..These data establish a signaling cascade in which regulated site-specific Lys-63-linked TRAF6 auto-ubiquitination is the critical upstream mediator of IKK...
  47. 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
    ..Thus, K63-linked polyubiquitination of proximal signaling proteins is a common mechanism used by diverse innate immune receptors for recruiting IKK and activating NF-kappaB...
  48. ncbi IRAK-M is a novel member of the Pelle/interleukin-1 receptor-associated kinase (IRAK) family
    H Wesche
    Tularik Inc, South San Francisco, California 94080, USA
    J Biol Chem 274:19403-10. 1999
    ..The discovery of IRAK-M adds another level of complexity to our understanding of signaling by members of the Toll/IL-1 receptor family...
  49. ncbi Interferon-alpha induction through Toll-like receptors involves a direct interaction of IRF7 with MyD88 and TRAF6
    Taro Kawai
    ERATO, Akira Innate Immunity Program, Japan Science and Technology Agency, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Nat Immunol 5:1061-8. 2004
    ..These results indicate that TLR-mediated IFN-alpha induction requires the formation of a complex consisting of MyD88, TRAF6 and IRF7 as well as TRAF6-dependent ubiquitination...
  50. ncbi TRAF6, a molecular bridge spanning adaptive immunity, innate immunity and osteoimmunology
    Hao Wu
    Department of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021, USA
    Bioessays 25:1096-105. 2003
    ..By virtue of its many signaling roles, TRAF6 represents an important target in the regulation of many disease processes, including immunity, inflammation and osteoporosis...
  51. pmc Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients
    Kaleb M Pauley
    Department of Oral Biology, University of Florida, Gainesville, Florida 32610, USA
    Arthritis Res Ther 10:R101. 2008
    ..In this study, the expression of selected microRNAs is examined in rheumatoid arthritis...
  52. ncbi TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasis
    Carolyn G King
    Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania 19104, USA
    Nat Med 12:1088-92. 2006
    ..These data identify a previously unrecognized role for TRAF6 in the maintenance of peripheral tolerance, and suggest the presence of a T cell-intrinsic control mechanism to render responder T cells susceptible to tolerizing signals...
  53. pmc The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells
    Cory Ahonen
    Department of Microbiology and Immunology, Dartmouth Medical School, 1 Medical Center Drive, Lebanon, NH 03756, USA
    Nat Immunol 3:451-6. 2002
    ..In addition, they define the roles that TRAF-dependent and TRAF-independent pathways play in regulating antigen-driven B cell differentiation...
  54. 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...
  55. ncbi Roles of TRAF6 in CD40 signaling
    Bruce S Hostager
    4 204 MEBRF, Department of Pediatrics, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
    Immunol Res 39:105-14. 2007
    ....
  56. pmc Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis
    N Kobayashi
    Department of Hematology, Research Institute, International Medical Center of Japan, Shinjuku ku, Tokyo 162 8655, Japan
    EMBO J 20:1271-80. 2001
    ..Thus, TRAF6 plays essential roles in both the differentiation and maturation of osteoclasts by activating various kinases via its multiple domains...
  57. ncbi Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways
    Ke Jun Han
    Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Sciences Center, Denver, Colorado 80206, USA
    J Biol Chem 279:15652-61. 2004
    ....
  58. pmc TRAF6 and the three C-terminal lysine sites on IRF7 are required for its ubiquitination-mediated activation by the tumor necrosis factor receptor family member latent membrane protein 1
    Shunbin Ning
    Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA
    Mol Cell Biol 28:6536-46. 2008
    ..This is the first evidence to imply that ubiquitination is required for phosphorylation and activation of a transcription factor...
  59. pmc Tumor necrosis factor receptor-associated factor 6 (TRAF6) stimulates extracellular signal-regulated kinase (ERK) activity in CD40 signaling along a ras-independent pathway
    M Kashiwada
    Department of Immunology, National Institute of Infectious Diseases, Tokyo, Japan
    J Exp Med 187:237-44. 1998
    ..These results suggest that CD40 activates ERK by both a Ras-dependent pathway and a Ras-independent pathway in which TRAF6 could be involved...
  60. ncbi TNF receptor-associated factor 6 is an essential mediator of CD40-activated proinflammatory pathways in monocytes and macrophages
    Lata Mukundan
    Department of Microbiology and Immunology, University of Louisville School of Medicine, Louisville, KY 40292, USA
    J Immunol 174:1081-90. 2005
    ..These data demonstrate that TRAF6 acts as a critical adapter of both the Src/ERK1/2 and IKK/NF-kappaB proinflammatory signaling pathways in monocytes and macrophages...
  61. pmc TANK potentiates tumor necrosis factor receptor-associated factor-mediated c-Jun N-terminal kinase/stress-activated protein kinase activation through the germinal center kinase pathway
    A I Chin
    Molecular Biology Institute, Jonsson Comprehensive Cancer Center, University of California Los Angeles, 90095, USA
    Mol Cell Biol 19:6665-72. 1999
    ..In addition, CD40 activated endogenous GCKR in primary B cells, implicating GCK family proteins in CD40-mediated B-cell functions...
  62. ncbi TRAF-1, -2, -3, -5, and -6 are induced in atherosclerotic plaques and differentially mediate proinflammatory functions of CD40L in endothelial cells
    Andreas Zirlik
    Donald W Reynolds Cardiovascular Research Center, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
    Arterioscler Thromb Vasc Biol 27:1101-7. 2007
    ..This study investigated the involvement of tumor necrosis factor receptor-associated factors (TRAFs) in CD40 signaling in endothelial cells (ECs) and their expression in atheromata and cells involved in atherogenesis...
  63. ncbi Characteristics and biological functions of TRAF6
    Jun ichiro Inoue
    Division of Cellular and Molecular Biology, Department of Cancer Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    Adv Exp Med Biol 597:72-9. 2007
    ..The role of TRAF6 in osteoclastogenesis and the molecular mechanisms ofTRAF6-mediated signal transduction are described in other chapters...
  64. pmc Identification of a consensus site for TRAF6/p62 polyubiquitination
    Trafina Jadhav
    Program in Cellular and Molecular Biosciences, Department of Biological Sciences, Auburn University, 331 Funchess Hall, Auburn, AL 36849, USA
    Biochem Biophys Res Commun 371:521-4. 2008
    ..These findings reveal a possible selection process for targeting a specific lysine residue by a single E3 ligase and underscore the role of the scaffold, p62, in this process...
  65. ncbi NF-kappaB is essential for induction of CYLD, the negative regulator of NF-kappaB: evidence for a novel inducible autoregulatory feedback pathway
    Hirofumi Jono
    Gonda Department of Cell and Molecular Biology, House Ear Institute, and Department of Otolaryngology, University of Southern California, Los Angeles, CA 90057, USA
    J Biol Chem 279:36171-4. 2004
    ..In addition, TRAF2 and TRAF6 appear to be differentially involved in NF-kappaB-dependent induction of CYLD by TNF-alpha and NTHi. These findings provide novel insights into the autoregulation of NF-kappaB activation...
  66. ncbi Inflammatory signaling pathway containing TRAF6 contributes to neointimal formation via diverse mechanisms
    Takuya Miyahara
    Department of Vascular Regeneration, Graduate School of Medicine, The University of Tokyo, 7 3 1 Hongo, Bunkyo, Tokyo 113 8655, Japan
    Cardiovasc Res 64:154-64. 2004
    ..The purpose of this study was to investigate the contribution of inflammatory signaling containing tumor necrosis factor receptor-associated factor 6 (TRAF6) to neointimal formation in a balloon injury model of rabbit carotid artery...
  67. ncbi ASK1 inhibits interleukin-1-induced NF-kappa B activity through disruption of TRAF6-TAK1 interaction
    Y Mochida
    Laboratory of Cell Signaling, Department of Hard Tissue Engineering, Division of Bio Matrix, Tokyo, Japan
    J Biol Chem 275:32747-52. 2000
    ..These results provide a new insight in the mode of action of MAPKKK family members; two distinct MAPKKKs in the same MAP kinase cascades directly interact and exert opposite effects in another signaling pathway, NF-kappaB...
  68. ncbi Tumor necrosis factor-alpha (TNF) stimulates RANKL-induced osteoclastogenesis via coupling of TNF type 1 receptor and RANK signaling pathways
    Y H Zhang
    Department of Orthopaedic Research, Barnes-Jewish Hospital at Washington University School of Medicine, St. Louis, Missouri 63110, USA
    J Biol Chem 276:563-8. 2001
    ..Our data suggest that exuberant TNF-induced osteoclastogensis is the result of coupling between RANK and TNFr1 and is dependent upon signals transmitted by the latter receptor...
  69. pmc Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-{alpha} induction
    Satoshi Uematsu
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita Osaka 565 0871, Japan
    J Exp Med 201:915-23. 2005
    ..These results indicated that IRAK-1 is a specific regulator for TLR7- and TLR9-mediated IFN-alpha induction in pDCs...
  70. ncbi Cutting edge: TNFR-associated factor (TRAF) 6 is essential for MyD88-dependent pathway but not toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta (TRIF)-dependent pathway in TLR signaling
    Jin Gohda
    Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
    J Immunol 173:2913-7. 2004
    ..These results indicate that TRAF6 is essential for MyD88-dependent signaling but is not required for TIR domain-containing adaptor-inducing IFN-beta (TRIF)-dependent signaling...
  71. ncbi VISA is an adapter protein required for virus-triggered IFN-beta signaling
    Liang Guo Xu
    Department of Immunology, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, Colorado 80206, USA
    Mol Cell 19:727-40. 2005
    ..These findings suggest that VISA is critically involved in both virus-triggered TLR3-independent and TLR3-mediated antiviral IFN signaling...
  72. pmc TRAF6-mediated ubiquitination regulates nuclear translocation of NRIF, the p75 receptor interactor
    Thangiah Geetha
    Department of Biological Sciences and Program in Cell and Molecular Biosciences, Auburn University, Auburn, AL, USA
    EMBO J 24:3859-68. 2005
    ..Finally, unlike wild-type NRIF, the K19R NRIF failed to reconstitute p75-mediated apoptosis in nrif-/- neurons. These results reveal a unique mechanism of p75 signaling and a novel role for K63-linked ubiquitin chains...
  73. pmc TRAF6 and MEKK1 play a pivotal role in the RIG-I-like helicase antiviral pathway
    Ryoko Yoshida
    Division of Molecular and Cellular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812 8582, Japan
    J Biol Chem 283:36211-20. 2008
    ..These data suggest that IPS-1 requires TRAF6 and MEKK1 to activate NF-kappaB and mitogen-activated protein kinases that are critical for the optimal induction of type I interferons...
  74. pmc The human toll signaling pathway: divergence of nuclear factor kappaB and JNK/SAPK activation upstream of tumor necrosis factor receptor-associated factor 6 (TRAF6)
    M Muzio
    Department of Immunology and Cell Biology, Mario Negri Institute, I 20157 Milan, Italy
    J Exp Med 187:2097-101. 1998
    ..Conversely, a dominant negative version of TRAF6 failed to block hToll-induced activation of stress-activated protein kinase/c-Jun NH2-terminal kinases, thus suggesting an early divergence of the two pathways...
  75. ncbi TRAF6 is a critical signal transducer in IL-33 signaling pathway
    Megumi Funakoshi-Tago
    Department of Biochemistry, Kyoritsu University of Pharmacy, 1 5 30 Shibakoen, Minato ku, Tokyo 105 8512, Japan
    Cell Signal 20:1679-86. 2008
    ..Thus, these data demonstrate that TRAF6 plays a pivotal role in IL-33 signaling pathway through its ubiquitin ligase activity...
  76. ncbi NOD2 pathway activation by MDP or Mycobacterium tuberculosis infection involves the stable polyubiquitination of Rip2
    Yibin Yang
    Department of Pathology, Case Western University School of Medicine, Cleveland, Ohio 44106, USA
    J Biol Chem 282:36223-9. 2007
    ..tuberculosis-induced Rip2 polyubiquitination appears MyD88-independent. Collectively, these data reveal that the NOD2 pathway is ubiquitin-regulated and that Rip2 employs a ubiquitin-dependent mechanism to achieve NF-kappaB activation...
  77. ncbi Variant IL-1 receptor-associated kinase-1 mediates increased NF-kappa B activity
    Gang Liu
    Department of Medicine, University of Alabama, Birmingham, AL 35294, USA
    J Immunol 179:4125-34. 2007
    ....
  78. pmc Ubiquitin-conjugating enzyme Ubc13 is a critical component of TNF receptor-associated factor (TRAF)-mediated inflammatory responses
    Toru Fukushima
    Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 104:6371-6. 2007
    ..These findings document a critical role for Ubc13 in inflammatory responses and suggest that agents reducing Ubc13 activity could have therapeutic utility...
  79. ncbi Caspase-8 regulation by direct interaction with TRAF6 in T cell receptor-induced NF-kappaB activation
    Nicolas Bidere
    Molecular Development Section, Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Curr Biol 16:1666-71. 2006
    ..Our results suggest that PKCtheta independently controls CARMA1 phosphorylation and BCL10-dependent caspase-8 activation and unveil an essential role for TRAF6 as a critical adaptor linking these two convergent signaling events...
  80. pmc Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain
    V Baud
    Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology, University of California, San Diego, School of Medicine, La Jolla, California 92093 0636 USA
    Genes Dev 13:1297-308. 1999
    ..TNF-alpha also enhances the binding of native TRAF2 to MEKK1 and stimulates the kinase activity of the latter. Thus, TNF-alpha and IL-1 signaling is based on oligomerization of TRAF2 and TRAF6 leading to activation of effector kinases...
  81. pmc Two differently regulated nuclear factor kappaB activation pathways triggered by the cytoplasmic tail of CD40
    N Tsukamoto
    Department of Oncology, The Institute of Medical Science, The University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Proc Natl Acad Sci U S A 96:1234-9. 1999
    ..These results indicate that NFkappaB activating signals emanating from cyt-N and cyt-C are mediated by the different members of the TRAF family and could be regulated in a distinct manner...
  82. ncbi Identification of TRAF6, a novel tumor necrosis factor receptor-associated factor protein that mediates signaling from an amino-terminal domain of the CD40 cytoplasmic region
    T Ishida
    Department of Oncology, The Institute of Medical Science, The University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108, Japan
    J Biol Chem 271:28745-8. 1996
    ..These results suggest that TRAF6 could mediate the CD40 signal that is transduced by the amino-terminal domain (230-245) of the CD40 cytoplasmic region and appears to be independent of other known TRAF family proteins...
  83. ncbi Toll/IL-1 receptor domain-containing adaptor inducing IFN-beta (TRIF) associates with TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates two distinct transcription factors, NF-kappa B and IFN-regulatory factor-3, in the Toll-like re
    Shintaro Sato
    Department of Host Defense, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
    J Immunol 171:4304-10. 2003
    ..Taken together, these results demonstrate that TRIF associates with TRAF6 and TBK1 independently, and activates two distinct transcription factors, NF-kappaB and IFN regulatory factor-3, respectively...
  84. ncbi Interleukin-8 up-regulation by neutrophil elastase is mediated by MyD88/IRAK/TRAF-6 in human bronchial epithelium
    D E Walsh
    Respiratory Research Division, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland
    J Biol Chem 276:35494-9. 2001
    ..These findings may have implications for therapeutic treatments in the cystic fibrosis condition...
  85. ncbi Differential regulation of interleukin 1 receptor and Toll-like receptor signaling by MEKK3
    Qiaojia Huang
    Department of Immunology, The University of Texas M D Anderson Cancer Center, Houston, Texas 77030, USA
    Nat Immunol 5:98-103. 2004
    ..Note: In the version of this article originally published online, the third author's name was incorrect. The correct author name should be Yong Lin. This error has been corrected for the HTML and print versions of this article...
  86. ncbi Crystal structure of the human ubiquitin conjugating enzyme complex, hMms2-hUbc13
    T F Moraes
    Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada
    Nat Struct Biol 8:669-73. 2001
    ..The structure of the hMms2-hUbc13 complex provides the conceptual foundation for understanding the mechanism of Lys 63 multiubiquitin chain assembly and for its interactions with the RING finger proteins Rad5 and Traf6...
  87. ncbi Role of the MyD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies
    Elena Raschi
    Istituto di Ricovero e Aura a Carattere Scientifico Istituto Auxologico Italiano, Allergy and Clinical Immunology Unit, Department of Internal Medicine, University of Milan, Italy
    Blood 101:3495-500. 2003
    ..Our findings demonstrate that anti-beta(2)-GPI antibodies react with their antigen likely associated to a member of the TLR/IL-1 receptor family on the EC surface and directly induce activation...
  88. ncbi The p62 scaffold regulates nerve growth factor-induced NF-kappaB activation by influencing TRAF6 polyubiquitination
    Marie W Wooten
    Department of Biological Sciences, Program in Cell and Molecular Biosciences, Auburn University, Alabama 36849, USA
    J Biol Chem 280:35625-9. 2005
    ..These results provide evidence for a mechanism whereby p62 serves to regulate the NF-kappaB pathway...
  89. ncbi TUCAN/CARDINAL and DRAL participate in a common pathway for modulation of NF-kappaB activation
    Romania Stilo
    BioGeM Consortium, Napoli, Italy
    FEBS Lett 521:165-9. 2002
    ..Thus, our observations suggest that DRAL and TUCAN/CARDINAL may participate in a regulatory mechanism that coordinates cellular responses controlled by NF-kappaB transcription factor...
  90. ncbi NF-kappaB activator Act1 associates with IL-1/Toll pathway adaptor molecule TRAF6
    Mutsumi Kanamori
    Laboratory for Genome Exploration Research Group, RIKEN Genomic Sciences Center, 1 7 22 Suehiro cho, Tsurumi ku, Yokohama 230 0045, Japan
    FEBS Lett 532:241-6. 2002
    ..Our results suggest that Act1 is involved in IL-1/Toll-mediated signaling through TRAF6...
  91. ncbi SIGIRR inhibits interleukin-1 receptor- and toll-like receptor 4-mediated signaling through different mechanisms
    Jinzhong Qin
    Department of Immunology, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    J Biol Chem 280:25233-41. 2005
    ..These results indicate that SIGIRR inhibits IL-1 and LPS signaling pathways through differential mechanisms...
  92. ncbi The C-terminal activating region 2 of the Epstein-Barr virus-encoded latent membrane protein 1 activates NF-kappaB through TRAF6 and TAK1
    Liming Wu
    Department of Biochemistry, Hong Kong University of Science and Technology, Clearwater Bay, Kowloon, Hong Kong, China
    J Biol Chem 281:2162-9. 2006
    ..Thus, LMP1 utilizes two distinct pathways to activate NF-kappaB: a major one through CTAR2/TRAF6/TAK1/IKKbeta (canonical pathway) and a minor one through CTAR1/TRAF3/NIK/IKKalpha (noncanonical pathway)...
  93. ncbi Divergence of apoptosis-inducing and preventing signals in bacteria-faced macrophages through myeloid differentiation factor 88 and IL-1 receptor-associated kinase members
    Klaus Ruckdeschel
    Max von Pettenkofer Institute for Hygiene and Medical Microbiology, Munich, Germany
    J Immunol 168:4601-11. 2002
    ....
  94. ncbi Physical and functional interaction of filamin (actin-binding protein-280) and tumor necrosis factor receptor-associated factor 2
    A Leonardi
    Immune Activation Section, Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892 1876, USA
    J Biol Chem 275:271-8. 2000
    ..Reintroduction of Filamin into these cells restores the TNF response. The data imply a role for Filamin in inflammatory signal transduction pathways...
  95. 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...
  96. ncbi Hepatitis C virus core protein activates nuclear factor kappa B-dependent signaling through tumor necrosis factor receptor-associated factor
    H Yoshida
    Department of Gastroenterology, Faculty of Medicine, University of Tokyo, Tokyo 113-8655, Japan
    J Biol Chem 276:16399-405. 2001
    ..In fact, HCV core protein activated interleukin-1beta promoter mainly through NF-kappaB pathway. Therefore, this function of HCV core protein may play an important role in the inflammatory reaction induced by this hepatotropic virus...
  97. ncbi Identification of a novel A20-binding inhibitor of nuclear factor-kappa B activation termed ABIN-2
    S Van Huffel
    Department of Molecular Biology, Unit for Molecular Signal Transduction in Inflammation, Flanders Interuniversity Institute for Biotechnology and Ghent University, 9000 Ghent, Belgium
    J Biol Chem 276:30216-23. 2001
    ..These results indicate that ABIN-2 interferes with NF-kappaB activation upstream of the IKK complex and that it might contribute to the NF-kappaB-inhibitory function of A20...
  98. ncbi The TFG protein, involved in oncogenic rearrangements, interacts with TANK and NEMO, two proteins involved in the NF-kappaB pathway
    Claudia Miranda
    Department of Experimental Oncology Operative Unit Molecular Mechanisms of Cancer Growth and Progression, Istituto Nazionale Tumori, Via G Venezian 1, Milan, Italy
    J Cell Physiol 208:154-60. 2006
    ..TFG enhances the effect of TNF-alpha, TANK, TNF receptor-associated factor (TRAF)2, and TRAF6 in inducing NF-kappaB activity. We suggest that TFG is a novel member of the NF-kappaB pathway...
  99. pmc Interleukin-1 (IL-1) receptor-associated kinase-dependent IL-1-induced signaling complexes phosphorylate TAK1 and TAB2 at the plasma membrane and activate TAK1 in the cytosol
    Zhengfan Jiang
    Department of Immunology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Mol Cell Biol 22:7158-67. 2002
    ..Taken together, the new data reveal that IRAK plays a critical role in mediating the association and dissociation of IL-1-induced signaling complexes, functioning as an organizer and transporter in IL-1-dependent signaling...
  100. ncbi Nuclear factor-kappaB regulates beta-cell death: a critical role for A20 in beta-cell protection
    David Liuwantara
    Arthritis and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
    Diabetes 55:2491-501. 2006
    ..These data demonstrate that A20 is the cardinal antiapoptotic gene in beta-cells. Further, A20 expression is NF-kappaB dependent, thus linking islet proinflammatory gene responses with protection from apoptosis...
  101. ncbi The CATERPILLER protein monarch-1 is an antagonist of toll-like receptor-, tumor necrosis factor alpha-, and Mycobacterium tuberculosis-induced pro-inflammatory signals
    Kristi L Williams
    Lineberger Comprehensive Cancer Center, Division of Infectious Diseases, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Biol Chem 280:39914-24. 2005
    ..Mutants containing the NBD-LRR or PyD-NBD also blocked IRAK-1 activation. This is the first example of a CLR protein that antagonizes inflammatory responses initiated by TLR agonists via interference with IRAK-1 activation...

Research Grants63

  1. FOXP3-microRNA146-NFkB Axis in Tumor Suppression
    Lizhong Wang; Fiscal Year: 2013
    ..abstract_text> ..
  2. In Vivo Function of TRAF6 As a Target of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    ....
  3. Negative regulation of NF-kB and inflammation by TAX1BP1
    Edward W Harhaj; Fiscal Year: 2012
    ..This proposal will provide mechanistic insight into how TAX1BP1, Itch and A20 function together to inactivate key signaling molecules and restrict inflammatory signaling pathways. ..
  4. GAMMA DELTA T CELLS IN LYME ARTHRITIS
    Ralph C Budd; Fiscal Year: 2011
    ..Understanding these interactions will improve our understanding of how ?? T cell regulate the immune response during infection and autoimmune conditions. ..
  5. The Role of Beta-Arrestins 1 and 2 in Rheumatoid Arthritis
    Hongkuan Fan; Fiscal Year: 2010
    ..abstract_text> ..
  6. MOLECULAR AND CELLULAR REGULATION OF TOLERANCE
    Yongwon Choi; Fiscal Year: 2010
    ..Thus, understanding molecular and cellular pathways that properly control immune responses will provide the foundation for novel intervention strategies to treat various chronic inflammatory diseases. ..
  7. Role and Mechanism of NLRX1-mediated Cell Stress Response in Insulin Resistance
    Haitao Wen; Fiscal Year: 2013
    ..Further studies could lead to the identification of new therapeutic targets and ultimately help develop rational, mechanism-based treatment strategies that target obesity and diabetes. ..
  8. Regulatory Mechanisms of Implant-Induced Osteolysis
    Yousef Abu-Amer; Fiscal Year: 2013
    ..Our proposal addresses novel questions and holds promise to identify novel selective anti-osteolytic therapies. ..
  9. Amelioration of Immune Cell-Mediated Periodontal Disease
    Toshihisa Kawai; Fiscal Year: 2012
    ....
  10. Understanding the early and late endosomal TLR9-mediated responses to viral DNA.
    Yong Jun Liu; Fiscal Year: 2013
    ..The third aim will focus on further characterization of three potential PACSIN1-interacting molecules including CD2AP, MEKK4 and TRAF4. ..
  11. TLR-mediated Signaling Complex Formation and Regulation of Effector Functions
    Hans Haecker; Fiscal Year: 2012
    ..e. autoimmune diseases and sepsis. ..
  12. Molecular Mechanisms Underlying Tak1 Function in Osteoclasts
    Yousef Abu-Amer; Fiscal Year: 2013
    ..2) Determine the mechanism by which TAK1 deletion regulates and impedes expression of TRAF6, NEMO and NICD. 3) Determine the effect of genetic ablation of NUMBL on the osteopetrotic phenotype of TAK1-null mice. ..
  13. Mechanisms of Protein Kinase Activation by Ubiquitin in the NF-kB Pathways
    Zhijian J Chen; Fiscal Year: 2013
    ..If successful, our research should reveal the fundamental mechanisms of NF-kB activation in immune and inflammatory responses and provide potential new approaches to inhibit aberrant NF-kB activation in human diseases. ..
  14. Diet-Environment Interactions in Inflammation
    Sanjay Rajagopalan; Fiscal Year: 2013
    ..The insights gleaned from these studies have significant public health ramifications and may eventually lead to appropriately designed human studies eventually culminating in policy changes to avert environmental exposure to PM2.5. ..
  15. The role of MCPIP1 in regulating NF-kB signaling and macrophage activation
    Mingui Fu; Fiscal Year: 2012
    ..abstract_text> ..
  16. TAK1/TRAF6 Signaling in Skeletal Muscle
    Ashok Kumar; Fiscal Year: 2013
    ..Successful completion of this project will provide critical insights into the signaling mechanisms and establish TAK1 and TRAF6 as novel molecular targets to prevent skeletal muscle loss in various muscular disorders. ..
  17. Toll-like Receptor Signaling in the Esophageal Epithelium
    Mei Lun Wang; Fiscal Year: 2013
    ....
  18. The Role of PLEKHM1 in Osteoclast Function
    Haibo Zhao; Fiscal Year: 2010
    ..We plan to determine how this new protein regulates the osteoclast, raising the possibility that we will be able to develop a new drug that prevents bone loss. ..
  19. The Role of Type III TGF-beta Receptor in the Fibrotic Tumor Stroma
    RACHEL HESLER; Fiscal Year: 2013
    ..These studies will determine the role of T?RIII in myofibroblast activation and ECM secretion, facilitating targeting of the fibrotic stroma for the treatment of these deadly cancers. ..
  20. Effect of Bacterial Tolerance on TLR4 Signal Transduction
    Andrei E Medvedev; Fiscal Year: 2013
    ..These advances would be of key importance for improving public health in septic patients in the U.S. ..
  21. Modulation of Oncogenic Signaling in Glioblastomas
    Shi Yuan Cheng; Fiscal Year: 2013
    ..abstract_text> ..
  22. DIFFERENTIATIVE SIGNALS FOR MACROPHAGE ACTIVATION
    Stefanie N Vogel; Fiscal Year: 2013
    ..Our findings will lead to development of new drugs that will increase the capacity of macrophages to kill bacteria and viruses more effectively or to prevent or repair damage to tissues caused by bacterial or viral infection. ..
  23. The Role of Ubiquitination on TBK1 Function
    Roosevelt Boursiquot; Fiscal Year: 2010
    ..A greater understanding of TBK1-mediated antiviral defense may suggest potential therapeutic targets in clinical applications. ..
  24. Identification and characterization of genes in del(5q) myelodysplastic syndrome
    Daniel Starczynowski; Fiscal Year: 2013
    ..Given that the molecular basis of MDS is poorly defined, we hope that characterization of TIFAB will facilitate understanding the molecular defects and the design of novel therapeutics in MDS. ..
  25. Redox Mediated Signaling in the Toll-like Receptor Family
    FREDRICK OAKLEY; Fiscal Year: 2010
    ..Eventually, this research could allow for the development of medical treatments to attenuate inflammation caused by LPS and other diseases involving inflammation. ..
  26. NKIP signaling and functions
    John Cambier; Fiscal Year: 2009
    ..Successful completion of these studies will provide important basis for understanding the biochemical and molecular mechanisms of NKIP action in inflammation and innate immunity against viral infection. ..
  27. Mechanisms of Alteration of B Lymphocyte Function by LMP1
    Gail A Bishop; Fiscal Year: 2013
    ..This project seeks to examine the mechanisms by which LMP1 affects B lymphocyte function, and how it mediates effects that contribute to pathogenesis of autoimmunity and B cell cancers. ..
  28. Metabolic Regulation of CD8 T Cell Memory Development
    Erika L Pearce; Fiscal Year: 2013
    ....
  29. RANK-Associated Inhibitor (RAIN) in Osteoclast Formation
    Bryant Darnay; Fiscal Year: 2007
    ..abstract_text> ..
  30. Regulation of Akt signaling activation by polyubiquitination
    Hui Kuan Lin; Fiscal Year: 2013
    ..Understanding the mechanism by which Akt activation is regulated may not only provide a great insight into how the oncogenic Akt signaling is regulated, but also offer the important therapeutic implications for human cancers. ..
  31. Epstein-Barr Virus LMP1-Mediated Oncogenecity
    Elliott D Kieff; Fiscal Year: 2013
    ..Our discoveries will elucidate new key targets in NFkB activation and more broadly advance priority target-based tool compound discovery. ..
  32. GENETIC BASES FOR DISEASES OF THE RANK SIGNALING PATHWAY
    STEVEN R MUMM; Fiscal Year: 2013
    ..The information gained from this study may also be useful for therapy in common bone diseases, such as osteoporosis. ..
  33. TRAF6 and the Fate of CD8 T Cells
    Yongwon Choi; Fiscal Year: 2013
    ....
  34. CYLD as a negative regulator for MUC5AC in NTHi-induced otitis media
    Erika Szymanski; Fiscal Year: 2007
    ..Understanding how mucus production is controlled in the middle ear will lay the foundation for new drugs that decrease mucus production and make ear infections less harmful. [unreadable] [unreadable] [unreadable]..
  35. MECHANISMS OF IGE SYNTHESIS BY B CELLS
    Raif Geha; Fiscal Year: 2007
    ..and c). the MAP kinases p38 and JNK. The results of the proposed studies should have an important impact on the understanding and treatment of allergic and immunologic diseases. ..
  36. The role of TRAF6 in the regulation of neurite outgrowth
    ANA LUISA JORDAO PERDIGOTO; Fiscal Year: 2010
    ..lacks intrinsic catalytic activity and relies on intracellular adaptor proteins to signal, such as TNF Receptor Associated Factor 6 (TRAF6)...
  37. Role of TRAF1 in signaling by TNFR2 family members
    Erdyni Tsitsikov; Fiscal Year: 2007
    ..We propose to determine the role of TRAF1 in OX40 signaling in vitro and in vivo.3. What is the role of TRAF1 in signaling by EBV LMP1? We will analyze the role of TRAF1 in EBV LMP1 signaling and B cell. ..
  38. Innate Immune Response Genes and P. Gingivalis
    Jenny Ting; Fiscal Year: 2009
    ..4) Cell lines with reduced ASC will also be tested. Since ASC can overcome the negative regulatory function of Monarch-1 and CIAS, ASC may enhance immune response to Pg to contain the infection. ..
  39. CYLD Regulation of Epidermal Growth and Neoplasia
    YUNYAN JENNIFER ZHANG; Fiscal Year: 2009
    ....
  40. Genetic and molecular analysis of Yersinia YopJ
    Neal Silverman; Fiscal Year: 2003
    ..By identifying the true targets of YopJ, new therapeutic means to treat the plague can be devised, thus reducing the potential impact of a bioterrorist attack. ..
  41. Induction of Macrophage iNOS by Salmonella
    BOBBY CHERAYIL; Fiscal Year: 2006
    ..The results of these studies will shed light on a novel function of SopE and SopE2 and will also improve understanding of the mechanisms that regulate iNOS expression. ..
  42. Cell-Based Assays for Identifying Anti-RANK Signaling Agents
    Xu Feng; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  43. Regulation of the Tp12 Kinase
    Philip Tsichlis; Fiscal Year: 2009
    ..Based on this information, we designed experiments that utilize molecular genetics, tissue culture technologies to address the mechanisms of Tpl2 activation by LPS and TNF-alpha. ..
  44. Structural biology of Toll like receptor/IL 1R signaling
    Liang Tong; Fiscal Year: 2005
    ..These will form the basis for further mutagenesis, biochemical, and functional studies to assess their importance. ..
  45. Genes in X-linked Ectodermal Dysplasia Receptor
    PREET CHAUDHARY; Fiscal Year: 2006
    ..In the long-term these studies may lead to better diagnosis and treatment of ectodermal dysplasias and craniofacial abnormalities. ..
  46. EPITHELIAL CELL CYTOKINE SECRETION BY INTEGRINS
    Dennis McGee; Fiscal Year: 2005
    ....
  47. IL17 RECEPTOR VARIANTS IN INTESTINAL EPITHELIAL CELLS
    Hans Christian Reinecker; Fiscal Year: 2002
    ..The purpose of our experiments will be to provide an increased understanding of the signal transduction of IL-17 ligand-receptor system and its role in regulation of human intestinal epithelial cell function. ..
  48. ROLE OF TAK1 IN RANKL SIGNALING PATHWAY
    Jun Ninomiya Tsuji; Fiscal Year: 2005
    ..These studies will advance the understanding of the molecular mechanisms underlying the osteoclastogenesis and may offer novel therapeutic targets for bone diseases caused by excessive osteoclastogenesis. ..
  49. In Vivo Function of NEMO As a Sensor of K63-Linked Polyubiquitination
    DEAN BALLARD; Fiscal Year: 2010
    ....
  50. TRAF6 regulation of NFAT
    Jennifer Gentry; Fiscal Year: 2006
    ..TRAF6 E3 ligase activity will be blocked by inhibiting the E2 ligase, Ubc13, in T cells and NFAT activation will then be examined. ..
  51. MECHANISMS OF SIGNAL INDUCED UBIQUITINATION OF IKBA
    Zhijian Chen; Fiscal Year: 2002
    ..abstract_text> ..
  52. Mechanisms of NF-kappaB Activation in T Lymphocytes
    Zhijian Chen; Fiscal Year: 2008
    ..Such knowledge is crucial to understanding and treating various human diseases, including MALT lymphoma and other immune disorders. ..
  53. Chemokines, nitric oxide, and myocardial depression
    Bysani Chandrasekar; Fiscal Year: 2005
    ..The results from these studies will further our knowledge of chemokine biology and lead to new therapeutic strategies to prevent or treat myocardial dysfunction in ischemia-reperfusion injury. ..
  54. Intracellular Signaling Triggered by Tall-1/BCMA
    Hong Bing Shu; Fiscal Year: 2005
    ..The genes and their protein products identified in this study may be used as molecular targets for drug development against certain immune-deficient and autoimmune diseases. ..
  55. Nitric Oxide Defense Against Porphyromonas gingivalis
    Robert Gyurko; Fiscal Year: 2006
    ..He is applying for the NIDCR Scholar Development and Faculty Transition Award to pursue scientific career as an independent investigator at Boston University School of Dental Medicine. [unreadable] [unreadable]..
  56. Regulation of HIV-1 Preintegration Complexes (PICs)
    RICHARD KORNBLUTH; Fiscal Year: 2002
    ..New tools and concepts will be gained, and precise molecular targets for anti-HIV drug design will come into focus. ..
  57. TRAF6 E3 LIGASE FUNCTION IN OSTEOCLASTOGENESIS
    Bryant G Darnay; Fiscal Year: 2010
    ..In particular, the data gathered from these experiments may provide insights to developing therapeutic strategies for a variety of bone related disease and possibly other diseases associated with immunity and inflammation ..
  58. Using gene targeting to address the role of LRRK2 in Parkinson's disease
    Bruce Hostager; Fiscal Year: 2007
    ..This knowledge will aid in the identification of the environmental triggers and additional genetic factors that participate in the development of Parkinson's disease. ..
  59. Toll-like Receptors and the Innate Immune Response
    THOMAS HAWN; Fiscal Year: 2003
    ..tuberculosis and L. major will reveal novel insights about innate immunity and infectious diseases that will have implications for vaccine development. ..
  60. STRUCTURAL STUDIES OF DEATH RECEPTOR SIGNALING
    Hao Wu; Fiscal Year: 2004
    ..The proposed research should shed light on the structural basis for the transduction of signals from receptors to downstream effectors by these proteins. ..
  61. Osteoclastogenesis and RANK signaling to NF-kB via TRAF6
    JASON BOCH; Fiscal Year: 2005
    ..A more detailed understanding of the basic regulation of osteoclastogenesis may permit development of potent novel therapeutics for treating periodontal disease and other inflammatory disorders associated with bone loss. ..
  62. Revitalizing Allografts for Craniofacial Reconstruction
    Edward Schwarz; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  63. RETINOIC ACID RECEPTOR GAMMA SPECIFIC SIGNALING IN MELAN
    REMCO SPANJAARD; Fiscal Year: 2004
    ..The result from these studies will allow the integration of the 3-D structure of RARg with its molecular and biological actions in relation to an important disease. ..