PMID- 8985011 OWN - NLM STAT- MEDLINE DCOM- 19970123 LR - 20211203 IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 275 IP - 5297 DP - 1997 Jan 10 TI - Activation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent pathway. PG - 200-3 AB - Interaction of the p55 tumor necrosis factor receptor 1 (TNF-R1)-associated signal transducer TRADD with FADD signals apoptosis, whereas the TNF receptor-associated factor 2 protein (TRAF2) is required for activation of the nuclear transcription factor nuclear factor kappa B. TNF-induced activation of the stress-activated protein kinase (SAPK) was shown to occur through a noncytotoxic TRAF2-dependent pathway. TRAF2 was both sufficient and necessary for activation of SAPK by TNF-R1; conversely, expression of a dominant-negative FADD mutant, which blocks apoptosis, did not interfere with SAPK activation. Therefore, SAPK activation occurs through a pathway that is not required for TNF-R1-induced apoptosis. FAU - Natoli, G AU - Natoli G AD - Fondazione Andrea Cesalpino and Istituto di I Clinica Medica, Policlinico Umberto I, Viale del Policlinico 155, 00161 Rome, Italy. FAU - Costanzo, A AU - Costanzo A FAU - Ianni, A AU - Ianni A FAU - Templeton, D J AU - Templeton DJ FAU - Woodgett, J R AU - Woodgett JR FAU - Balsano, C AU - Balsano C FAU - Levrero, M AU - Levrero M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Carrier Proteins) RN - 0 (FADD protein, human) RN - 0 (Fas-Associated Death Domain Protein) RN - 0 (Free Radical Scavengers) RN - 0 (NF-kappa B) RN - 0 (Proteins) RN - 0 (Reactive Oxygen Species) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (Recombinant Proteins) RN - 0 (TNF Receptor-Associated Factor 1) RN - 0 (TNF Receptor-Associated Factor 2) RN - 0 (Tumor Necrosis Factor-alpha) RN - 1CC1JFE158 (Dactinomycin) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.25 (MAP Kinase Kinase Kinase 1) RN - EC 2.7.11.25 (MAP3K1 protein, human) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/pharmacology MH - *Adaptor Proteins, Signal Transducing MH - Apoptosis MH - Calcium-Calmodulin-Dependent Protein Kinases/*metabolism MH - Carrier Proteins/metabolism MH - Cell Line MH - Dactinomycin/pharmacology MH - Enzyme Activation MH - Fas-Associated Death Domain Protein MH - Free Radical Scavengers/pharmacology MH - HeLa Cells MH - Humans MH - JNK Mitogen-Activated Protein Kinases MH - *MAP Kinase Kinase Kinase 1 MH - *Mitogen-Activated Protein Kinases MH - NF-kappa B/metabolism MH - Protein Serine-Threonine Kinases/metabolism MH - Proteins/*metabolism MH - Reactive Oxygen Species/metabolism MH - Receptors, Tumor Necrosis Factor/*metabolism MH - Recombinant Proteins/pharmacology MH - Signal Transduction MH - TNF Receptor-Associated Factor 1 MH - TNF Receptor-Associated Factor 2 MH - Transfection MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 1997/01/10 00:00 MHDA- 1997/01/10 00:01 CRDT- 1997/01/10 00:00 PHST- 1997/01/10 00:00 [pubmed] PHST- 1997/01/10 00:01 [medline] PHST- 1997/01/10 00:00 [entrez] AID - 10.1126/science.275.5297.200 [doi] PST - ppublish SO - Science. 1997 Jan 10;275(5297):200-3. doi: 10.1126/science.275.5297.200.