tnf receptor associated factor 2

Summary

Summary: A signal transducing tumor necrosis factor receptor associated factor that is involved in TNF RECEPTOR feedback regulation. It is similar in structure and appears to work in conjunction with TNF RECEPTOR-ASSOCIATED FACTOR 1 to inhibit APOPTOSIS.

Top Publications

  1. pmc Epstein-Barr virus-encoded latent membrane protein 1 activates the JNK pathway through its extreme C terminus via a mechanism involving TRADD and TRAF2
    A G Eliopoulos
    CRC Institute for Cancer Studies, The University of Birmingham Medical School, Birmingham B15 2TA, England
    J Virol 73:1023-35. 1999
  2. ncbi The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination
    Andrew Kovalenko
    Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel
    Nature 424:801-5. 2003
  3. ncbi TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways
    H Hsu
    Tularik, Incorporated, South San Francisco, California 94080, USA
    Cell 84:299-308. 1996
  4. ncbi The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins
    M Rothe
    Department of Molecular Biology Tularik, Incorporated, South San Francisco, California 94080, USA
    Cell 83:1243-52. 1995
  5. ncbi Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB
    Thijn R Brummelkamp
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Nature 424:797-801. 2003
  6. ncbi The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family
    G Mosialos
    Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115
    Cell 80:389-99. 1995
  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. pmc The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation
    H Y Song
    Tularik, Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 93:6721-5. 1996
  9. 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
  10. pmc TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1-TRAF2 complex to sensitize tumor cells to TNFalpha
    James E Vince
    Department of Biochemistry, La Trobe University, Kingsbury Drive, Melbourne, VIC 3086, Australia
    J Cell Biol 182:171-84. 2008

Detail Information

Publications209 found, 100 shown here

  1. pmc Epstein-Barr virus-encoded latent membrane protein 1 activates the JNK pathway through its extreme C terminus via a mechanism involving TRADD and TRAF2
    A G Eliopoulos
    CRC Institute for Cancer Studies, The University of Birmingham Medical School, Birmingham B15 2TA, England
    J Virol 73:1023-35. 1999
    ..These data further define a role for TRADD and TRAF2 in JNK activation and confirm that LMP1 utilizes signalling mechanisms used by the TNF receptor/CD40 family to elicit its pleiotropic activities...
  2. ncbi The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination
    Andrew Kovalenko
    Department of Biological Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel
    Nature 424:801-5. 2003
    ..Truncations of CYLD found in cylindromatosis result in reduced enzymatic activity, indicating a link between impaired deubiquitination of CYLD substrates and human pathophysiology...
  3. ncbi TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways
    H Hsu
    Tularik, Incorporated, South San Francisco, California 94080, USA
    Cell 84:299-308. 1996
    ..Thus, these two TNFR1-TRADD signaling cascades appear to bifurcate at TRADD...
  4. ncbi The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins
    M Rothe
    Department of Molecular Biology Tularik, Incorporated, South San Francisco, California 94080, USA
    Cell 83:1243-52. 1995
    ..The recruitment of c-IAP1 or c-IAP2 to the TNFR2 signaling complex requires a TRAF2-TRAF1 heterocomplex...
  5. ncbi Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB
    Thijn R Brummelkamp
    Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Nature 424:797-801. 2003
    ..We show that this effect can be relieved by aspirin derivatives that inhibit NF-kappaB activity, which suggests a therapeutic intervention strategy to restore growth control in patients suffering from familial cylindromatosis...
  6. ncbi The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family
    G Mosialos
    Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115
    Cell 80:389-99. 1995
    ..The interaction of LMP1 with these TNFR family-associated proteins is further evidence for their role in signaling and links LMP1-mediated transformation to signal transduction from the TNFR family...
  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. pmc The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation
    H Y Song
    Tularik, Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 93:6721-5. 1996
    ..Our findings suggest a possible molecular mechanism that could explain A20's ability to negatively regulate its own TNF-inducible expression...
  9. 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...
  10. pmc TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1-TRAF2 complex to sensitize tumor cells to TNFalpha
    James E Vince
    Department of Biochemistry, La Trobe University, Kingsbury Drive, Melbourne, VIC 3086, Australia
    J Cell Biol 182:171-84. 2008
    ..Lysosomal degradation of cIAP1-TRAF2 by TWEAK/FN14 therefore critically alters the balance of life/death signals emanating from TNF-R1 in immortalized cells...
  11. ncbi IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis
    James E Vince
    Department of Biochemistry, La Trobe University, Kingsbury Drive, Melbourne, VIC 3086, Australia
    Cell 131:682-93. 2007
    ..Cells treated with an IAC, or those in which cIAP1 was deleted, became sensitive to apoptosis induced by exogenous TNFalpha, suggesting novel uses of these compounds in treating cancer...
  12. ncbi TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40
    M Rothe
    Molecular Biology Department, Tularik, Inc, South San Francisco, CA 94080, USA
    Science 269:1424-7. 1995
    ..A truncated derivative of TRAF2 lacking an amino-terminal RING finger domain was a dominant-negative inhibitor of NF-kappa B activation mediated by TNF-R2 and CD40. Thus, TRAF2 is a common mediator of TNF-R2 and CD40 signaling...
  13. ncbi TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2
    Xiaoming Li
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nature 416:345-7. 2002
    ..These findings identify a physiologic role for c-IAP1 and define a mechanism by which TNF-RII-regulated ubiquitin protein ligase activity can potentiate TNF-induced apoptosis...
  14. ncbi Anatomy of TRAF2. Distinct domains for nuclear factor-kappaB activation and association with tumor necrosis factor signaling proteins
    M Takeuchi
    Yamanouchi Pharmaceutical Co Ltd, Tsukuba, Ibaraki 305, Japan
    J Biol Chem 271:19935-42. 1996
    ..Thus, distinct domains of TRAF2 are involved in recruitment and signaling functions...
  15. ncbi Apoptotic crosstalk of TNF receptors: TNF-R2-induces depletion of TRAF2 and IAP proteins and accelerates TNF-R1-dependent activation of caspase-8
    Mariola Fotin-Mleczek
    Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
    J Cell Sci 115:2757-70. 2002
    ..Hence, TNF-R2 triggering can interfere with TNF-R1-induced apoptosis by inhibition of NF-kappaB-dependent production of anti-apoptotic factors and by blocking the action of anti-apoptotic factors at the post-transcriptional level...
  16. ncbi Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death
    K Tada
    Department of Immunology, Juntendo University, School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo 113 8421, Japan
    J Biol Chem 276:36530-4. 2001
    ..Collectively, these results indicate that both TRAF2 and TRAF5 are involved in TNF-induced NF-kappaB activation and protection from cell death...
  17. ncbi A novel family of putative signal transducers associated with the cytoplasmic domain of the 75 kDa tumor necrosis factor receptor
    M Rothe
    Department of Molecular Biology, Genentech, Incorporated, South San Francisco, California 94080
    Cell 78:681-92. 1994
    ..TRAF1 interacts with TNF-R2 indirectly through heterodimer formation with TRAF2...
  18. 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
    ....
  19. pmc Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma
    Jonathan J Keats
    Comprehensive Cancer Center, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
    Cancer Cell 12:131-44. 2007
    ..These results highlight the critical importance of the NF-kappaB pathway in the pathogenesis of multiple myeloma...
  20. ncbi TRAF2 deficiency results in hyperactivity of certain TNFR1 signals and impairment of CD40-mediated responses
    L T Nguyen
    Department of Immunology, University of Toronto, Ontario, Canada
    Immunity 11:379-89. 1999
    ..These data demonstrate two important roles of TRAF2, one as a negative regulator of certain TNFR1 signals and the other as a positive mediator of CD40 signaling...
  21. pmc PKC phosphorylation of TRAF2 mediates IKKalpha/beta recruitment and K63-linked polyubiquitination
    Shitao Li
    Department of Pathology, Harvard Medical School, Boston, MA 02115, USA
    Mol Cell 33:30-42. 2009
    ....
  22. ncbi Structural basis for self-association and receptor recognition of human TRAF2
    Y C Park
    Department of Biochemistry, The Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, New York 10021, USA
    Nature 398:533-8. 1999
    ..The trimeric structure of the TRAF domain provides an avidity-based explanation for the dependence of TRAF recruitment on the oligomerization of the receptors by their trimeric extracellular ligands...
  23. ncbi Tumor necrosis factor receptor-associated factor (TRAF) 5 and TRAF2 are involved in CD30-mediated NFkappaB activation
    S Aizawa
    Department of Pathology, The Institute of Medical Science, The University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108, Japan
    J Biol Chem 272:2042-5. 1997
    ..Taken together, our results indicate that TRAF2 and TRAF5 directly interact with CD30 and are involved in NFkappaB activation by CD30 signaling...
  24. pmc Crystallographic analysis of CD40 recognition and signaling by human TRAF2
    S M McWhirter
    Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720 3206, USA
    Proc Natl Acad Sci U S A 96:8408-13. 1999
    ..The spacing between the CD40 binding sites on TRAF2 supports an elegant signaling mechanism in which trimeric, extracellular ligands preorganize the receptors to simultaneously recognize three sites on the TRAF trimer...
  25. pmc Ubiquitination and translocation of TRAF2 is required for activation of JNK but not of p38 or NF-kappaB
    Hasem Habelhah
    Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY, USA
    EMBO J 23:322-32. 2004
    ..Altogether, our findings highlight a novel mechanism of TRAF2-dependent activation of diverse signaling cascades that is impaired in Hodgkin-Reed-Sternberg cells...
  26. pmc Cloning and expression of apoptosis inhibitory protein homologs that function to inhibit apoptosis and/or bind tumor necrosis factor receptor-associated factors
    A G Uren
    The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia
    Proc Natl Acad Sci U S A 93:4974-8. 1996
    ....
  27. pmc The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation
    Sharron A N Brown
    Vascular Biology Department, Jerome H Holland Laboratory for the Biomedical Sciences, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855, USA
    Biochem J 371:395-403. 2003
    ..These results indicate that Fn14 is a functional TWEAK receptor that can associate with four distinct TRAF family members and stimulate the NF-kappaB transcription factor signalling pathway...
  28. ncbi The cytokine-inducible zinc finger protein A20 inhibits IL-1-induced NF-kappaB activation at the level of TRAF6
    K Heyninck
    Department of Molecular Biology, Flanders Interuniversity Institute for Biotechnology and University of Ghent, Belgium
    FEBS Lett 442:147-50. 1999
    ..More importantly, we present evidence that A20 interferes with IL-1-induced NF-kappaB activation at the level of TRAF6, upstream of NIK. Moreover, A20 was shown to directly interact with TRAF6...
  29. pmc Structural basis for the lack of E2 interaction in the RING domain of TRAF2
    Qian Yin
    Weill Medical College of Cornell University, New York, New York 10021, USA
    Biochemistry 48:10558-67. 2009
    ..Our structural observation should prompt a re-evaluation of the role of TRAF2 in TNFalpha signaling and may indicate that TRAF2-associated proteins such as cIAPs may be the ubiquitin ligases for NF-kappaB signaling...
  30. 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...
  31. pmc TNF-alpha induced c-IAP1/TRAF2 complex translocation to a Ubc6-containing compartment and TRAF2 ubiquitination
    Chuan Jin Wu
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    EMBO J 24:1886-98. 2005
    ..Therefore, the ER plays a key role in the TNF-R-mediated signal transduction cascade by acting as a site of assembly for E2/E3/substrate complexes...
  32. pmc Differential signaling and tumor necrosis factor receptor-associated factor (TRAF) degradation mediated by CD40 and the Epstein-Barr virus oncoprotein latent membrane protein 1 (LMP1)
    K D Brown
    Medical Scientist Training Program, University of Iowa, Iowa City 52242, USA
    J Exp Med 193:943-54. 2001
    ..This suggests that LMP1 utilizes a modified CD40 signaling pathway. Failure to regulate TRAFs may contribute to the enhanced capacity of LMP1 to activate B cells as well as promote B cell transformation...
  33. ncbi Caveolin-1 associates with TRAF2 to form a complex that is recruited to tumor necrosis factor receptors
    X Feng
    Interdepartmental Program in Vascular Biology and Transplantation, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06536 0812, USA
    J Biol Chem 276:8341-9. 2001
    ..These findings suggest that intracellular distribution of activated TNF receptors may be regulated by caveolin-1 via its interaction with TRAF2...
  34. ncbi Nuclear factor kB-independent cytoprotective pathways originating at tumor necrosis factor receptor-associated factor 2
    G Natoli
    Fondazione Andrea Cesalpino, Policlinico Umberto I, University of Rome La Sapienza, Viale del Policlinico 155, 00161 Rome, Italy
    J Biol Chem 273:31262-72. 1998
    ..Our results indicate that TNF-induced cytoprotection is a complex function requiring the integration of multiple signal transduction pathways...
  35. 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...
  36. ncbi Caspase-cleaved TRAF1 negatively regulates the antiapoptotic signals of TRAF2 during TNF-induced cell death
    H D Jang
    Division of Molecular Life Science and Center for Cell Signalling Research, Ewha Womans University, Seoul, 120 750, Korea
    Biochem Biophys Res Commun 281:499-505. 2001
    ..These results indicate that caspase-dependent cleavage of TRAF1 generates TRAF1-c fragments that are able to bind TRAF2, and then sequester TRAF2 from the TNF-R1 complex, rendering cells, at least in part, sensitive to TNF...
  37. ncbi TRAF3 forms heterotrimers with TRAF2 and modulates its ability to mediate NF-{kappa}B activation
    Liusheng He
    Flow Cytometry Section in the Office of Science and Technology, National Institute of Arthritis and Musculoskeletal and Skin Diseases NIH, 9000 Rockville Pike, Building 10, Bethesda, MD 20892, USA
    J Biol Chem 279:55855-65. 2004
    ..Together, these results reveal a novel association between TRAF2 and TRAF3 that is mediated by unique portions of each protein and that specifically regulates activation of NF-kappaB, but not AP-1...
  38. ncbi Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling
    Pu Xia
    Division of Human Immunology, The Hanson Institute, Institute of Medical and Veterinary Science and University of Adelaide, Frome Road, Adelaide SA 5000, Australia
    J Biol Chem 277:7996-8003. 2002
    ..These findings show a role for SphK in the signal transduction by TRAF2 specifically leading to activation of NF-kappa B and antiapoptosis...
  39. ncbi The structural basis for the recognition of diverse receptor sequences by TRAF2
    H Ye
    Department of Biochemistry, Weill Medical College, New York, New York, USA
    Mol Cell 4:321-30. 1999
    ..The structural information provides a template for the further dissection of receptor binding specificity of TRAF2 and for the understanding of the complexity of TRAF-mediated signal transduction...
  40. ncbi Recruitment of tumor necrosis factor receptor-associated factor family proteins to apoptosis signal-regulating kinase 1 signalosome is essential for oxidative stress-induced cell death
    Takuya Noguchi
    Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, CREST, Japan
    J Biol Chem 280:37033-40. 2005
    ..A novel signaling complex including TRAF2, TRAF6, and ASK1 may thus be the key component in oxidative stress-induced cell death...
  41. ncbi Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling
    Ramin Massoumi
    Department of Molecular Medicine, Max Planck Institute of Biochemistry, D 82152 Martinsried, Germany
    Cell 125:665-77. 2006
    ....
  42. ncbi Translocation of TRAF proteins regulates apoptotic threshold of cells
    R H Arch
    Gwen Knapp Center for Lupus and Immunology Research, Howard Hughes Medical Institute, Department of Medicine, University of Chicago, IL 60637, USA
    Biochem Biophys Res Commun 272:936-45. 2000
    ..The ratio between soluble and insoluble TRAF2 determines the sensitivity of cells to TNF-alpha-induced apoptosis and may play an important role in limiting further TRAF-dependent signal transduction...
  43. ncbi Presence of a new conserved domain in CART1, a novel member of the tumor necrosis factor receptor-associated protein family, which is expressed in breast carcinoma
    C H Regnier
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM ULP, C U de Strasbourg, France
    J Biol Chem 270:25715-21. 1995
    ..Moreover, in these malignant cells, the CART1 protein is localized in the nucleus. Altogether, these observations indicate that CART1 may be involved in TNF-related cytokine signal transduction in breast carcinoma...
  44. pmc Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear factor-kappaB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2
    H Y Song
    Tularik, Two Corporate Drive, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 94:9792-6. 1997
    ..Thus, TRAF2 is the bifurcation point of two kinase cascades leading to activation of NF-kappaB and JNK, respectively...
  45. ncbi Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein assoc
    T Yuasa
    Diabetes Research Laboratory, Medical Services, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    J Biol Chem 273:22681-92. 1998
    ..Thus, TRAF2 initiates SAPK and p38 activation by binding two proximal protein kinases: GCK and RIP. GCK and RIP, in turn, signal by binding MAPKKKs upstream of the SAPKs and p38s...
  46. pmc Tumor necrosis factor receptor-associated factor (TRAF)-1, TRAF-2, and TRAF-3 interact in vivo with the CD30 cytoplasmic domain; TRAF-2 mediates CD30-induced nuclear factor kappa B activation
    S Ansieau
    Department of Internal Medicine III, University of Ulm Medical Center, Germany
    Proc Natl Acad Sci U S A 93:14053-8. 1996
    ..These data indicate that CD30 cross-linking-induced NF-kappa B activation is predominantly TRAF-2-mediated...
  47. ncbi Multiple carboxyl-terminal regions of the EBV oncoprotein, latent membrane protein 1, cooperatively regulate signaling to B lymphocytes via TNF receptor-associated factor (TRAF)-dependent and TRAF-independent mechanisms
    L K Busch
    Molecular Biology Graduate Program, University of Iowa, Iowa City, IA 52242, USA
    J Immunol 167:5805-13. 2001
    ..Furthermore, we find that the function of CTAR1, but not CTAR2, correlates with TRAF binding and present evidence that as yet unidentified cytoplasmic proteins may associate with LMP1 to mediate some of its signaling activities...
  48. 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...
  49. pmc T cell receptor-dependent cell death of T cell hybridomas mediated by the CD30 cytoplasmic domain in association with tumor necrosis factor receptor-associated factors
    S Y Lee
    Howard Hughes Medical Institute, Rockefeller University, New York 10021, USA
    J Exp Med 183:669-74. 1996
    ..These results indicate that TRAF1 and/or TRAF2 play an important role in cell death in addition to their previously identified roles in cell proliferation...
  50. ncbi TRAF2 and TRAF3 signal adapters act cooperatively to control the maturation and survival signals delivered to B cells by the BAFF receptor
    Sandra Gardam
    Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst NSW 2010, Australia
    Immunity 28:391-401. 2008
    ..This process was TRAF2 dependent, revealing dual roles for TRAF2 in regulating B cell homeostasis...
  51. ncbi Tumor necrosis factor (TNF)-induced germinal center kinase-related (GCKR) and stress-activated protein kinase (SAPK) activation depends upon the E2/E3 complex Ubc13-Uev1A/TNF receptor-associated factor 2 (TRAF2)
    Chong Shan Shi
    B Cell Molecular Immunology Section, Laboratory of Immunoregulation, NIAID, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 278:15429-34. 2003
    ..These results indicate that the assembly of a TRAF2 lysine 63-linked polyubiquitin chain by Ubc13/Uev1A is required for TNF-mediated GCKR and SAPK activation, but may not be required for ASK1 activation...
  52. 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...
  53. 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...
  54. ncbi MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1
    N L Malinin
    Department of Membrane Research and Biophysics, The Weizmann Institute of Science, Rehovot, Israel
    Nature 385:540-4. 1997
    ..It also blocked NF-kappaB induction by interleukin-1. Our findings indicate that NIK participates in an NF-kappaB-inducing signalling cascade common to receptors of the TNF/NGF family and to the interleukin-1 type-I receptor...
  55. ncbi Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice
    W C Yeh
    Amgen Institute, Department of Medical Biophysics, University of Toronto, Ontario, Canada
    Immunity 7:715-25. 1997
    ..These results suggest that TRAF2-independent pathways of NF-kappaB activation exist and that TRAF2 is required for an NF-kappaB-independent signal that protects against TNF-induced apoptosis...
  56. ncbi Physiological roles and mechanisms of signaling by TRAF2 and TRAF5
    Ping Yee Billie Au
    Campbell Family for Breast Cancer Research, University Health Network and Department of Medical Biophysics, University of Toronto, Toranto, Ontario, Canada
    Adv Exp Med Biol 597:32-47. 2007
    ..TRAF2 is heavily regulated by ubiquitin signals, and many of the signaling functions of TRAF2 are mediated through its RING domain and likely its own role as an E3 ubiquitin ligase...
  57. ncbi NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation
    C Y Wang
    Department of Endodontics, School of Dentistry, Lineberger Comprehensive Cancer Center, and Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599 7295, USA
    Science 281:1680-3. 1998
    ..Thus, NF-kappaB activates a group of gene products that function cooperatively at the earliest checkpoint to suppress TNF-alpha-mediated apoptosis and that function more distally to suppress genotoxic agent-mediated apoptosis...
  58. ncbi Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling
    Bruce S Hostager
    Department of Pediatrics, Interdisciplinary Program in Immunology, University of Iowa, Iowa City 52242, USA
    J Biol Chem 278:45382-90. 2003
    ..These findings demonstrate previously unappreciated roles for TRAF2 in signaling by TNF receptor family members, using an approach that facilitates the analysis of genes critical to the viability of whole organisms...
  59. pmc Posttranscriptional downregulation of c-IAP2 by the ubiquitin protein ligase c-IAP1 in vivo
    Dietrich B Conze
    Laboratory of Immune Cell Biology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 3002, Bethesda, MD 20892, USA
    Mol Cell Biol 25:3348-56. 2005
    ..Thus, the c-IAPs represent a pair of TNFR-associated ubiquitin protein ligases in which one regulates the expression of the other by a posttranscriptional and E3-dependent mechanism...
  60. 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...
  61. pmc I-TRAF is a novel TRAF-interacting protein that regulates TRAF-mediated signal transduction
    M Rothe
    Tularik, Inc, South San Francisco, CA 94080, USA
    Proc Natl Acad Sci U S A 93:8241-6. 1996
    ..Overexpression of I-TRAF inhibits TRAF2-mediated NF-kappa B activation signaled by CD40 and both TNF receptors. Thus, I-TRAF appears as a natural regulator of TRAF function that may act by maintaining TRAFs in a latent state...
  62. ncbi TRAF2 differentially regulates the canonical and noncanonical pathways of NF-kappaB activation in mature B cells
    Adrian P Grech
    Centenary Institute of Cancer Medicine and Cell Biology, Locked Bag No 6, Newtown, NSW 2042, Australia
    Immunity 21:629-42. 2004
    ..This dual functionality explains the contrasting roles of TRAF2 in B cell maturation and activation...
  63. pmc N-terminal fragment of c-FLIP(L) processed by caspase 8 specifically interacts with TRAF2 and induces activation of the NF-kappaB signaling pathway
    Takao Kataoka
    Division of Bioinformatics, Center for Biological Resources and Informatics, Tokyo Institute of Technology, Midori ku, Yokohama 226 8501, Japan
    Mol Cell Biol 24:2627-36. 2004
    ..Thus, our present results demonstrate that FLIP(p43) processed by caspase 8 specifically interacts with TRAF2 and subsequently induces activation of the NF-kappaB signaling pathway...
  64. ncbi The kinase activity of Rip1 is not required for tumor necrosis factor-alpha-induced IkappaB kinase or p38 MAP kinase activation or for the ubiquitination of Rip1 by Traf2
    Thomas H Lee
    Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    J Biol Chem 279:33185-91. 2004
    ..Finally, recruitment of the ubiquitinated Tak1 complex is dependent on the presence of Rip1, suggesting that Rip1 ubiquitination rather than its phosphorylation is critical in signaling...
  65. ncbi The inhibitor of apoptosis protein fusion c-IAP2.MALT1 stimulates NF-kappaB activation independently of TRAF1 AND TRAF2
    Eugene Varfolomeev
    Departments of Protein Engineering and Physiological Chemistry, Genentech, Inc, South San Francisco, California 94110, USA
    J Biol Chem 281:29022-9. 2006
    ..Therefore, the t(11, 18)(q21;q21) translocation creating the c-IAP2.MALT1 fusion protein activates NF-kappaB and contributes to human malignancy in the absence of signaling adaptors that might otherwise regulate its activity...
  66. ncbi Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B
    I K Jang
    Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis 46202 5120, USA
    Biochem Biophys Res Commun 242:613-20. 1998
    ..4-1BB-mediated NF-kappa B activation was inhibited by a dominant negative-TRAF2 or -NF-kappa B-inducing kinase (NIK). These data suggest that 4-1BB functions may be mediated by NF-kappa B activation, which requires a TRAF2/NIK pathway...
  67. ncbi Cooperation between TNF receptor-associated factors 1 and 2 in CD40 signaling
    Ping Xie
    Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA
    J Immunol 176:5388-400. 2006
    ....
  68. pmc A regulatory role for TRAF1 in antigen-induced apoptosis of T cells
    D E Speiser
    Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, Toronto, Ontario M5G 2M9, Canada
    J Exp Med 185:1777-83. 1997
    ....
  69. ncbi Cutting edge: contrasting roles of TNF receptor-associated factor 2 (TRAF2) and TRAF3 in CD40-activated B lymphocyte differentiation
    B S Hostager
    Department of Microbiology, University of Iowa, VA Medical Center, Iowa City 52242, USA
    J Immunol 162:6307-11. 1999
    ..In contrast, TRAF2 appears to play a positive role in B cell differentiation, and this activity is apparent even when its binding site on CD40 is disrupted...
  70. 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...
  71. ncbi TANK, a co-inducer with TRAF2 of TNF- and CD 40L-mediated NF-kappaB activation
    G Cheng
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Genes Dev 10:963-73. 1996
    ..We propose that ligand binding to CD40 or TNFR II leads to the formation of a TRAF2/TANK complex, mediating NF-kappaB activation...
  72. pmc Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in the Hodgkin-Reed-Sternberg cells
    Ryouichi Horie
    Division of Pathology, Department of Cancer Research, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
    Am J Pathol 160:1647-54. 2002
    ..Thus, cytoplasmic aggregation of TRAF proteins appears to reflect constitutive CD30 signaling which is characteristic of H-RS cells...
  73. pmc TRAF-interacting protein (TRIP): a novel component of the tumor necrosis factor receptor (TNFR)- and CD30-TRAF signaling complexes that inhibits TRAF2-mediated NF-kappaB activation
    S Y Lee
    The Rockefeller University, New York 10021, USA
    J Exp Med 185:1275-85. 1997
    ..Thus, TRIP acts as a receptor-proximal regulator that may influence signals responsible for cell activation/proliferation and cell death induced by members of the TNFR superfamily...
  74. 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...
  75. pmc Tumor necrosis factor receptor associated factor 2 is a mediator of NF-kappa B activation by latent infection membrane protein 1, the Epstein-Barr virus transforming protein
    K M Kaye
    Department of Medicine, Brigham and Women s Hospital, Harvard Medical School, Boston, MA, USA
    Proc Natl Acad Sci U S A 93:11085-90. 1996
    ....
  76. ncbi Distinct BIR domains of cIAP1 mediate binding to and ubiquitination of tumor necrosis factor receptor-associated factor 2 and second mitochondrial activator of caspases
    Temesgen Samuel
    Burnham Institute for Medical Research, La Jolla, CA 92037, USA
    J Biol Chem 281:1080-90. 2006
    ....
  77. ncbi Dissection of B cell differentiation during primary immune responses in mice with altered CD40 signals
    Teruhito Yasui
    Department of Molecular Immunology, Research Institute for Microbial Diseases, Osaka University, 3 1 Yamada oka, Suita, Osaka 565 0871, Japan
    Int Immunol 14:319-29. 2002
    ..We conclude that combinations of these two signals determine which of the extrafollicular or the follicular (GC) differentiation pathway B cells enter...
  78. ncbi Ligand-independent signaling by overexpressed CD30 drives NF-kappaB activation in Hodgkin-Reed-Sternberg cells
    Ryouichi Horie
    Division of Pathology, The Institute of Medical Science, The University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    Oncogene 21:2493-503. 2002
    ..Inhibition of NF-kappaB activation by adenovirus vector-mediated gene transfer may provide a novel strategy of cell- and target molecule-specific therapy for patients with HD...
  79. ncbi Expression of TNF receptors and related signaling molecules in the bone marrow from patients with myelodysplastic syndromes
    Masakazu Sawanobori
    Department of Pathology and Immunology, Aging and Developmental Sciences, Division of Gerontology and Gerodontology, Graduate School, Tokyo Medical and Dental University, 1 5 45 Yushima, Bunkyo ku, 113 8519, Tokyo, Japan
    Leuk Res 27:583-91. 2003
    ....
  80. ncbi Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis
    Jun Kuai
    Musculoskeletal Science and Protein Chemistry and Proteomics, Wyeth Research, Cambridge, Massachusetts 02140, USA
    J Biol Chem 278:14363-9. 2003
    ..Their association with LT beta R was further confirmed by coimmunoprecipitation in U937 cells and HEK293 cells. The presence of cIAP1 and Smac in LIGHT.LT beta R complex revealed a novel mechanism of LIGHT.LT beta R-induced apoptosis...
  81. ncbi The NPM-ALK oncoprotein abrogates CD30 signaling and constitutive NF-kappaB activation in anaplastic large cell lymphoma
    Ryouichi Horie
    Fourth Department of Internal Medicine, Faculty of Medicine, Kitasato University, 1 15 1 Kitasato, Sagamihara, Kanagawa 228 8555, Japan
    Cancer Cell 5:353-64. 2004
    ..Thus, NPM-ALK abrogates CD30-driven NF-kappaB activation and can also induce an ALCL phenotype, distinguishing ALCL cells from H-RS cells of T cell origin...
  82. 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...
  83. ncbi The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor
    B R Wong
    Laboratory of Immunology, The Rockefeller University, New York, New York 10021, USA
    J Biol Chem 273:28355-9. 1998
    ..Furthermore, transfection experiments with TRANCE-R deletion mutants revealed that multiple regions of the TRANCE-R can mediate NF-kappaB activation...
  84. pmc The in vivo function of a noncanonical TRAF2-binding domain in the C-terminus of CD40 in driving B-cell growth and differentiation
    Li Fan Lu
    Department of Microbiology and Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, Lebanon, NH 03756, USA
    Blood 110:193-200. 2007
    ..This study demonstrates a new functional domain in CD40 that controls critical aspects of B-cell immunity in an in vivo setting...
  85. pmc CD30-dependent degradation of TRAF2: implications for negative regulation of TRAF signaling and the control of cell survival
    C S Duckett
    Howard Hughes Medical Institute, Gwen Knapp Center for Lupus and Immunology Research, and Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
    Genes Dev 11:2810-21. 1997
    ..These studies provide a potential mechanism through which CD30, as well as other TRAF-binding members of the TNFR superfamily, can negatively regulate cell survival...
  86. ncbi Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily
    L M Boucher
    Department of Medical Biophysics, University of Toronto, Ontario, Canada
    Biochem Biophys Res Commun 233:592-600. 1997
    ..We show that these amino acid motifs are conserved in TNFRp75 and CD40 and that sequences in these receptors homologous to TRAF-binding sequences found in CD30 can selectively bind the TRAFs in a predictable manner...
  87. pmc Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling
    Sivakumar Vallabhapurapu
    Laboratory of Gene Regulation and Signal Transduction, Departments of Pharmacology and Pathology, Cancer Center, University of California, San Diego, California 93093, USA
    Nat Immunol 9:1364-70. 2008
    ..Constitutive activation of this pathway causes perinatal lethality and lymphoid defects...
  88. ncbi Activation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent pathway
    G Natoli
    Fondazione Andrea Cesalpino and Istituto di I Clinica Medica, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy
    Science 275:200-3. 1997
    ..Therefore, SAPK activation occurs through a pathway that is not required for TNF-R1-induced apoptosis...
  89. ncbi A novel RING finger protein interacts with the cytoplasmic domain of CD40
    H M Hu
    Department of Pathology, University of Michigan Medical School, Ann Arbor 48109
    J Biol Chem 269:30069-72. 1994
    ..This is the first identification of a molecule that interacts with CD40 and whose sequence suggests a potential role in signaling...
  90. ncbi CD30 contains two binding sites with different specificities for members of the tumor necrosis factor receptor-associated factor family of signal transducing proteins
    R W Gedrich
    Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, Chicago, Illinois 60637, USA
    J Biol Chem 271:12852-8. 1996
    ....
  91. ncbi Involvement of CRAF1, a relative of TRAF, in CD40 signaling
    G Cheng
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    Science 267:1494-8. 1995
    ..It is likely that other members of the TNF receptor superfamily use CRAF-related proteins in their signal transduction processes...
  92. 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...
  93. ncbi Death deflected: IL-15 inhibits TNF-alpha-mediated apoptosis in fibroblasts by TRAF2 recruitment to the IL-15Ralpha chain
    S Bulfone-Paus
    Institute of Immunology, Department of Urology, Department of Pathology, University Hospital Benjamin Franklin, Free University, Berlin, Germany
    FASEB J 13:1575-85. 1999
    ..Thus, IL-15Ralpha chain stimulation is a powerful deflector of cell death very early in the apoptosis signaling cascade, while TNF-alpha and IL-15 surface as major opponents in apoptosis control...
  94. ncbi Recruitment of CD40 and tumor necrosis factor receptor-associated factors 2 and 3 to membrane microdomains during CD40 signaling
    B S Hostager
    Departments of Microbiology and Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA
    J Biol Chem 275:15392-8. 2000
    ....
  95. ncbi Rapid CD40-mediated rescue from CD95-induced apoptosis requires TNFR-associated factor-6 and PI3K
    Rebecca J Benson
    Medical Scientist Training Program and Immunology Graduate Program, University of Iowa and Veterans Affairs Medical Center, Iowa City 52245, USA
    Eur J Immunol 36:2535-43. 2006
    ..In contrast, CD40 rescue was completely abrogated in TRAF6-deficient B cells, which showed reduced activation of Akt in response to CD40 engagement. These results reveal a new rapid mechanism to balance B cell activation and apoptosis...
  96. ncbi A novel mechanism of TRAF signaling revealed by structural and functional analyses of the TRADD-TRAF2 interaction
    Y C Park
    Department of Biochemistry, Weill Medical College and Graduate School of Medical Sciences of Cornell University, New York, New York 10021, USA
    Cell 101:777-87. 2000
    ..The stronger affinity and unique specificity of the TRADD-TRAF2 interaction are crucial for the suppression of apoptosis and provide a mechanistic basis for the perturbation of TRAF recruitment in sensitizing cell death induction...
  97. pmc TNF receptor-associated factor (TRAF) domain and Bcl-2 cooperate to induce small B cell lymphoma/chronic lymphocytic leukemia in transgenic mice
    Juan M Zapata
    The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 101:16600-5. 2004
    ..Given that many human chronic lymphocytic leukemias overexpress TRAF1 and Bcl-2, our findings suggest that cooperation between Bcl-2 and TRAF pathways contributes to the development of this type of leukemia...
  98. ncbi Signaling and protein associations of a cell permeable CD40 complex in B cells
    Stephen J Zoog
    Department of Immunology and Inflammation, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, CT 06877, USA
    Mol Immunol 40:681-94. 2004
    ..We present a novel approach for delivering pre-activated, soluble receptor cytoplasmic domains into cells and recovering intact signaling complexes for molecular analysis...
  99. ncbi Caspase-mediated cleavage converts the tumor necrosis factor (TNF) receptor-associated factor (TRAF)-1 from a selective modulator of TNF receptor signaling to a general inhibitor of NF-kappaB activation
    Frank Henkler
    Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany
    J Biol Chem 278:29216-30. 2003
    ....
  100. ncbi TNF-related weak inducer of apoptosis receptor, a TNF receptor superfamily member, activates NF-kappa B through TNF receptor-associated factors
    Songyi Han
    Division of Molecular Life Sciences and Center for Cell Signaling Research, Ewha Womans University, 11 1 Daehyun Dong, Seoul 120 750, Republic of Korea
    Biochem Biophys Res Commun 305:789-96. 2003
    ..Furthermore, TweakR mutations within the TRAF-binding motif abolished TweakR-stimulated SMC migration, revealing a role for TRAFs in TweakR-induced activation events...
  101. ncbi Tumor necrosis factor-alpha-induced IKK phosphorylation of NF-kappaB p65 on serine 536 is mediated through the TRAF2, TRAF5, and TAK1 signaling pathway
    Hiroaki Sakurai
    Department of Pathogenic Biochemistry, Institute of Natural Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama 930 0194, Japan
    J Biol Chem 278:36916-23. 2003
    ....

Research Grants62

  1. 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. ..
  2. 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. ..
  3. Heat Shock-Induced Apoptosis
    Shawn B Bratton; Fiscal Year: 2012
    ..Thus, it is anticipated that the work proposed herein will significantly improve our understanding of how heat shock works in the clinic and may shed light on new pathways that can be exploited therapeutically in the future. ..
  4. CYTOPROTECTIVE EFFECTS OF INFLAMMATION MEDIATED MEMBRANE REPAIR
    DOUGLAS LOWELL MANN; Fiscal Year: 2013
    ..abstract_text> ..
  5. Cytoprotective cytokine signaling and reperfusion injury
    DOUGLAS LOWELL MANN; Fiscal Year: 2010
    ....
  6. BTK SIGNALING IN B CELL SURVIVAL BY BAFF-R
    Wasif N Khan; Fiscal Year: 2011
    ..The proposed research will illuminate novel mechanisms by which Btk regulates B cell survival critical for normal B cell survival in the healthy immune system as well as B cell autoimmune and immunodeficiency diseases. ..
  7. The role of MCPIP1 in regulating NF-kB signaling and macrophage activation
    Mingui Fu; Fiscal Year: 2012
    ..abstract_text> ..
  8. Non-coding RNAs at the interface of aberrant NF-kB signals and lymphomagenesis
    RICARDO C AGUIAR; Fiscal Year: 2013
    ..Finally, as the potential of inhibiting and restoring miRNA levels with therapeutic intent is becoming a reality, our studies may provide a blueprint for testing this concept in cancer. ..
  9. Role of Mixed Lineage Kinase 3/SPRK in Stress Signaling
    AJAY NMN RANA; Fiscal Year: 2010
    ..Furthermore, the results from these studies will aide in the development of novel pharmacological approaches towards increasing the efficiency and specificity of chemo- or radio- sensitization for cancer therapies. ..
  10. Impact of the interferon regulated proteins XAF1 and ZNF313 on innate immunity
    Douglas W Leaman; Fiscal Year: 2010
    ....
  11. Mechanisms by which LMP-1 Regulates Lineage Commitment in Mesenchymal Stem Cells
    FRANCES LOUISA TITUS; Fiscal Year: 2013
    ..abstract_text> ..
  12. Exosomal TRAF2-CSN5 complex mediated inflammation promotes tumor growth
    Huang Ge Zhang; Fiscal Year: 2013
    ....
  13. Sphingosine Kinases in Cancer Cell Signaling
    Sarah Spiegel; Fiscal Year: 2013
    ..abstract_text> ..
  14. lung tumor exosome-mediated inflammation promotes tumor progression and growth
    Huang Ge Zhang; Fiscal Year: 2010
    ..abstract_text> ..
  15. Viral and Genetic Regulation of Abnormal OCL Activity in PD
    DEBORAH LYNN GALSON; Fiscal Year: 2012
    ..responsible for MVNP and p62p392L effects on OCL formation outlined above" will provide important insight into the pathogenesis of PD and are directly linked to the cellular and in vivo studies proposed in Project 2, ..
  16. 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. ..
  17. 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. ..
  18. RANK-Associated Inhibitor (RAIN) in Osteoclast Formation
    Bryant Darnay; Fiscal Year: 2007
    ..abstract_text> ..
  19. Integration of TNF Signaling in Apoptosis
    Anning Lin; Fiscal Year: 2010
    ..abstract_text> ..
  20. 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. ..
  21. Myofibroblasts, T cells and malignant cells interplay in breast cancer metastasis
    Weizhou Zhang; Fiscal Year: 2013
    ..The proposed studies are innovative as they address a poorly explored and controversial research problem with great clinical significance and public health importance. ..
  22. 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. ..
  23. CD40 SIGNAL TRANSDUCTION
    Claudius Vincenz; Fiscal Year: 1999
    ..Specific Aim 3: Determine if CD40bp and TRAF2 modulate other CD40 signaling events including activation of cytoplasmic src-like kinases and PI3 kinase. ..
  24. CONTROL OF TNF SIGNALING BY NFKB
    ALBERT BALDWIN JR; Fiscal Year: 2003
    ..These experiments will provide new insight into mechanisms whereby TNFalpha initiates and controls critical pathways involved in mediating inflammatory, proliferative and apoptotic functions. ..
  25. CYLD Regulation of Epidermal Growth and Neoplasia
    YUNYAN JENNIFER ZHANG; Fiscal Year: 2009
    ....
  26. Regulation of TNFa signaling
    Anning Lin; Fiscal Year: 2013
    ....
  27. Inositol hexakisphosphate kinase 2:apoptosis regulator
    Daniel Lindner; Fiscal Year: 2006
    ..Determine the relevance of IP6K2 domains for IFN- beta-therapy in vivo - Assess IP6K2 mutants grownas xenografts. ..
  28. TNFR ASSOCIATED FACTOR IN PULMONARY RESPONSE TO TNF-A
    Gloria Pryhuber; Fiscal Year: 2003
    ..The proposed studies will demonstrate the cellular function of TRAF1 in vitro and the role of TRAF1 expression in vivo in transgenic overexpression and ablation models stressed by hyperoxia. ..
  29. 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. ..
  30. ASSEMBLY/REGULATION OF CD40 RECEPTOR COMPLEX IN B CELLS
    Randolph Noelle; Fiscal Year: 2001
    ..Studies are proposed which will evaluate if engagement of one TNFR family member can prohibit the recruitment of TRAFs by other family members; and what the functional consequences of receptor desensitization are to the B-cell. ..
  31. Comprehensive Candidate Pathway Analysis in SLE
    Patrick Gaffney; Fiscal Year: 2009
    ..abstract_text> ..
  32. Caveolae in Insulin Signaling
    CYNTHIA MASTICK; Fiscal Year: 2007
    ..3. Examine the link between caveolin phosphorylation and metabolic regulation in vivo through the creation of fat-specific caveolin-1 and caveolin-1/Y14F knock-in mice. ..
  33. MOLECULAR MECHANISMS OF CD30+ LYMPHOMA GROWTH
    Eckhard Podack; Fiscal Year: 2002
    ..by CD30-L gene ablation to eliminate CD30-L triggered CD30 signals and signaling by CD30 induction on ongoing immune responses to tumors in vivo and in vitro. ..
  34. TRANSCRIPTIONAL CONTROL OF HUMAN T CELL RECEPTOR GENES
    Laurie Glimcher; Fiscal Year: 2009
    ..abstract_text> ..
  35. Regulation of TRAF2 Activity in Normal and Tumor Cells
    Hasem Habelhah; Fiscal Year: 2009
    ..Our work will shed new light on the regulation of TRAF2 phosphorylation by PKC and Akt and their role in the regulation of tumor cell resistance to stress-induced cell death. ..
  36. Role of Programmed Necrosis in Immune Responses
    Francis Chan; Fiscal Year: 2006
    ..Moreover, controlling cell death may offer a novel approach to treating autoimmune diseases. [unreadable] [unreadable]..
  37. Identifying small molecule inhibitors of KSHV vFLIP-TRAF2 interactions.
    Ethel Cesarman; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  38. 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. ..
  39. A caspase-8 substrate in T cell activation
    Ralph Budd; Fiscal Year: 2009
    ..We propose c-FLIPL as both the activator of caspase and the critical caspase-8 substrate in T cell activation. ..
  40. Selective Disruptive of TNFalpha Signaling in Murine CIA
    Robert Scheinman; Fiscal Year: 2002
    ..By extension, these data will help us understand more fully the mechanisms of action of TNF alpha blocking drugs and potentially will identify new targets for future arthritis therapies. ..
  41. Regulation of Cellular Response to TNF
    Xiangwei Wu; Fiscal Year: 2009
    ..abstract_text> ..
  42. Pre-association and Signaling by TNF-like Receptors
    Francis Chan; Fiscal Year: 2003
    ..The second part of this proposal attempts to elucidate the mechanism by which TNFR coordinates the recruitment of these signaling proteins. ..
  43. MOUSE MODELS TO STUDY MULIBREY NANISM
    Juan Zapata; Fiscal Year: 2005
    ..study the developmental and phenotypic alterations of trim37 knock out and FINmajor-mutated trim37 mice. These mice will be the foundation for further studies on the biology and etiology of Mulibrey Nanism. ..
  44. How Anthrax lethal factor kills activated macrophages
    Michael Karin; Fiscal Year: 2003
    ..anthracis and its host, this project should enable the design of new therapeutic strategies that will tilt the balance in favor of the host macrophage in the battle against B. anthracis and inhalation anthrax. ..
  45. Patterns of gene expression in Mulibrey Nanism
    Juan Zapata; Fiscal Year: 2005
    ..Specific Aim 2, is there any alteration in the patterns of gene expression induced by cytokines in normal and Mulibrey Nanism fibroblasts? Specific Aim 3, what is the role of TRIM37 in regulating gene expression? ..
  46. Functions and Mechanisms of Radiation Induced Responses
    Michael Karin; Fiscal Year: 2006
    ..abstract_text> ..
  47. INTERACTIONS OF HEAVY METAL IONS WITH THE HUMAN GENOME
    Michael Karin; Fiscal Year: 2007
    ..As NF-KB plays a key role in inflammation, understanding the regulation of IKK activity by oxidants, such as ozone, will provide a molecular basis for oxidant induced inflammatory disease. ..
  48. TRAF Regulation and Receptor Interactions in TNFR Family Signals
    GAIL BISHOP; Fiscal Year: 2009
    ..To explore the role of TRAF5 in B cell activation. ..
  49. How Anthrax lethal factor kills macrophages
    Michael Karin; Fiscal Year: 2008
    ..Interference with this activation process may be used to increase host resistance to bacterial infections, both with agents of bioterrorism and more common pathogens. ..
  50. MOUSE MODELS TO STUDY THE ROLE OF TRAF1 AND TRAF2 IN THE ETIOLOGY OF LEUKEMIA
    Juan Zapata; Fiscal Year: 2007
    ..Characterization of the CLL-like lymphoproliferative disorder caused by overexpression of TRAF2DN and Bcl-2 in B cells. [unreadable] [unreadable] [unreadable] [unreadable]..
  51. 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. ..
  52. Molecular Epidemiology of non-Hodgkin Lymphoma Survival
    James R Cerhan; Fiscal Year: 2010
    ..Host genetics may also lead to a better understanding of NHL pathophysiology that could lead to new approaches to improve the survival of NHL patients. ..
  53. Modulation of Apoptosis by IRF-4 in EBV transformation
    Luwen Zhang; Fiscal Year: 2010
    ..These experiments may identify the apoptosis. These experiments may identify critical mechanisms that IRF-4 uses to prevent apoptosis in EBV-transformed cells. ..
  54. 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. ..
  55. ACTIVATION OF IKB KINASE BY HTLV-I TAX
    Shao Cong Sun; Fiscal Year: 2003
    ..abstract_text> ..
  56. Interferon Regulatory Factor 7 and NPC
    Luwen Zhang; Fiscal Year: 2006
    ..This study would lead to a better understanding of how LMP-1 and IRF-7 interact to participate in viral pathogenesis, latency, and transformation. ..
  57. 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. ..
  58. Inhibiting JNK A New Anti-Inflammatory Strategy
    Wang Min; Fiscal Year: 2010
    ..We will study the effects of a novel scaffolding protein AIP1, on vascular endothelium. Our work may lead to better tests and treatments for atherosclerosis patients. ..
  59. NIK KINASE AND T CELL COSTIMULATION
    Shao Cong Sun; Fiscal Year: 2003
    ..It is also expected that novel signaling molecules will have been isolated which function in the T cell co-stimulatory pathway. ..
  60. Molecular Mechanisms Mediating NF-kB2/p100 Processing
    Shao Cong Sun; Fiscal Year: 2007
    ..abstract_text> ..
  61. BLyS, APRIL and antibody production in HIV infection
    Andrea Cerutti; Fiscal Year: 2004
    ..Aim 1. To analyze the mechanisms by which HIV up-regulates BLyS and APRIL in APCs. Aim 2. To analyze the role of BLyS and APRIL in the modulation of HIV-induced antibody production. ..
  62. Immunogenetics of Non-Hodgkin Lymphoma Survival
    James Cerhan; Fiscal Year: 2006
    ..abstract_text> ..