PMID- 11729181 OWN - NLM STAT- MEDLINE DCOM- 20020228 LR - 20210209 IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 277 IP - 5 DP - 2002 Feb 1 TI - Phorbol 12-myristate 13-acetate inhibits death receptor-mediated apoptosis in Jurkat cells by disrupting recruitment of Fas-associated polypeptide with death domain. PG - 3776-83 AB - Regulation of death receptor-mediated apoptosis is incompletely understood. Previous studies have demonstrated that phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, inhibits Fas (CD95)-mediated apoptosis in Jurkat (type II) cells but not SKW6.4 (type I) cells. In this study, we demonstrated that PMA also protects Jurkat cells from apoptosis induced by tumor necrosis factor-alpha and the tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL). Interestingly, PMA failed to protect Jurkat cells from apoptosis induced by other agents, including etoposide, camptothecin, and gamma-irradiation. Analysis of the initial events induced by agonistic anti-Fas antibodies revealed that PMA inhibited Fas binding to Fas-associated polypeptide with death domain (FADD) in Jurkat cells but not in SKW6.4 cells. Although the protein kinase inhibitor bisindoylmaleimide VIII increased apoptosis induced by agonistic anti-Fas antibody, tumor necrosis factor-alpha, and TRAIL, these effects were not observed with the protein kinase C inhibitor H7 and were not associated with increased FADD recruitment to Fas. These results indicate that PMA inhibits death signaling induced by a number of discrete receptors and suggest that the effects are mediated at the level of receptor-mediated adaptor molecule recruitment. FAU - Meng, Xue Wei AU - Meng XW AD - Division of Oncology Research, Department of Molecular Pharmacology, Mayo Clinic, Mayo Graduate School, Rochester, Minnesota 55905, USA. FAU - Heldebrant, Michael P AU - Heldebrant MP FAU - Kaufmann, Scott H AU - Kaufmann SH LA - eng GR - R01 CA069008/CA/NCI NIH HHS/United States GR - R01 CA69008/CA/NCI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. DEP - 20011129 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 0 (Adaptor Proteins, Signal Transducing) RN - 0 (Antigens, CD) RN - 0 (Apoptosis Regulatory Proteins) RN - 0 (Carrier Proteins) RN - 0 (FADD protein, human) RN - 0 (Fas-Associated Death Domain Protein) RN - 0 (HSP90 Heat-Shock Proteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 0 (TNFRSF10A protein, human) RN - 0 (TNFSF10 protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (fas Receptor) RN - 6PLQ3CP4P3 (Etoposide) RN - 98600C0908 (Cycloheximide) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) RN - XT3Z54Z28A (Camptothecin) SB - IM MH - *Adaptor Proteins, Signal Transducing MH - Antigens, CD/drug effects/physiology MH - Apoptosis/*drug effects/radiation effects MH - Apoptosis Regulatory Proteins MH - Binding Sites MH - Camptothecin/toxicity MH - Carrier Proteins/*antagonists & inhibitors MH - Cell Line MH - Cycloheximide/pharmacology MH - Etoposide/toxicity MH - Fas-Associated Death Domain Protein MH - Gamma Rays MH - HSP90 Heat-Shock Proteins/physiology MH - Humans MH - Jurkat Cells MH - Kinetics MH - Membrane Glycoproteins/pharmacology MH - Receptors, TNF-Related Apoptosis-Inducing Ligand MH - Receptors, Tumor Necrosis Factor/*antagonists & inhibitors MH - TNF-Related Apoptosis-Inducing Ligand MH - Tetradecanoylphorbol Acetate/*pharmacology MH - Tumor Cells, Cultured MH - Tumor Necrosis Factor-alpha/pharmacology MH - fas Receptor/drug effects/*physiology EDAT- 2001/12/01 10:00 MHDA- 2002/03/01 10:01 CRDT- 2001/12/01 10:00 PHST- 2001/12/01 10:00 [pubmed] PHST- 2002/03/01 10:01 [medline] PHST- 2001/12/01 10:00 [entrez] AID - S0021-9258(20)87673-X [pii] AID - 10.1074/jbc.M107218200 [doi] PST - ppublish SO - J Biol Chem. 2002 Feb 1;277(5):3776-83. doi: 10.1074/jbc.M107218200. Epub 2001 Nov 29.