title: Translocation of TRAF proteins regulates apoptotic threshold of cells.
abstract: Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) are involved in signaling pathways triggered by members of the TNF receptor (TNFR) family and other cell surface proteins. After recruitment to a receptor, TRAFs initiate formation of multiprotein complexes that induce downstream events, such as translocation of transcription factor nuclear factor kappaB (NF-kappaB) and activation of c-Jun N-terminal kinase (JNK). Several proteins in these complexes play important roles in regulation of apoptosis. However, the fate of TRAF-containing complexes once assembled in response to receptor multimerization is not understood. In this report, we demonstrate that crosslinking of TNFR family members or interaction of TRAF2 with the cytoplasmic protein A20 leads to intracellular translocation of TRAF2. This redistribution leads to depletion of the cytoplasmic pool of TRAF2. 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.
authors.affiliation: Gwen Knapp Center for Lupus and Immunology Research, Howard Hughes Medical Institute, Department of Medicine, University of Chicago, IL 60637, USA. rarch@im.wustl.edu
authors.forename: R H
authors.initials: RH
authors.lastname: Arch
authors.forename: R W
authors.initials: RW
authors.lastname: Gedrich
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson
mesh_terms: D015703:Antigens, CD; D017209:Apoptosis / Q000187:drug effects; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins; D003850:Deoxyribonuclease I / Q000378:metabolism; D004361:Drug Tolerance; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D017730:Ki-1 Antigen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins; D009994:Osmolar Concentration; D011485:Protein Binding / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D047992:TNF Receptor-Associated Factor 2; D014162:Transfection; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics / Q000378:metabolism; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D015703:Antigens, CD; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017730:Ki-1 Antigen; D016328:NF-kappa B; D009687:Nuclear Proteins; D011506:Proteins; D017475:Receptors, Nerve Growth Factor; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D047992:TNF Receptor-Associated Factor 2; C505716:TNFRSF4 protein, human; C505714:TNFRSF9 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014409:Tumor Necrosis Factor-alpha; D003850:Deoxyribonuclease I; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3