title: Caspase-cleaved TRAF1 negatively regulates the antiapoptotic signals of TRAF2 during TNF-induced cell death.
abstract: Tumor necrosis factor (TNF) signaling leads to pleiotropic responses in a wide range of cell types, in part by activating antiapoptotic and proapoptotic pathways. Previous studies have suggested that TNF receptor-associated factor (TRAF) 2 can mediate crucial antiapoptotic signals during TNF stimulation. However, it is unclear how the antiapoptotic signals via TRAF2 in TNF-R1 signaling is regulated. Here we show that TRAF1 is cleaved by caspase-8 into two fragments during apoptosis induced by TNF. Overexpression of the C-terminal cleavage product, TRAF1-c, increased TNF-induced cell death of hybridoma T cells. Importantly, we demonstrate that the cleavage product of TRAF1 coimmunoprecipitates with TRAF2 that is released from the TNF-R1 complex in response to prolonged TNF treatment. 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.
authors.affiliation: Division of Molecular Life Science and Center for Cell Signalling Research, Ewha Womans University, Seoul, 120-750, Korea.
authors.forename: H D
authors.initials: HD
authors.lastname: Jang
authors.forename: Y M
authors.initials: YM
authors.lastname: Chung
authors.forename: J H
authors.initials: JH
authors.lastname: Baik
authors.forename: Y G
authors.initials: YG
authors.lastname: Choi
authors.forename: I S
authors.initials: IS
authors.lastname: Park
authors.forename: Y K
authors.initials: YK
authors.lastname: Jung
authors.forename: S Y
authors.initials: SY
authors.lastname: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001665:Binding Sites; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D004274:DNA, Recombinant; D004305:Dose-Response Relationship, Drug; D006801:Humans; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D004274:DNA, Recombinant; D011506:Proteins; D018124:Receptors, Tumor Necrosis Factor; D047990:TNF Receptor-Associated Factor 1; D047992:TNF Receptor-Associated Factor 2; D014409:Tumor Necrosis Factor-alpha; D020169:Caspases