Phorbol 12-myristate 13-Acetate Inhibits Death Receptor-mediated Apoptosis in Jurkat Cells by Disrupting Recruitment of Fas-associated Polypeptide with Death Domain
| Autor: | Scott H. Kaufmann, Michael P. Heldebrant, Xue Wei Meng |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Fas-Associated Death Domain Protein
Apoptosis Biochemistry Jurkat cells Receptors Tumor Necrosis Factor Fas ligand Cell Line TNF-Related Apoptosis-Inducing Ligand Jurkat Cells Antigens CD Tumor Cells Cultured Humans HSP90 Heat-Shock Proteins fas Receptor FADD Cycloheximide Molecular Biology Protein kinase C Adaptor Proteins Signal Transducing Etoposide Death domain Binding Sites Membrane Glycoproteins biology Tumor Necrosis Factor-alpha Chemistry Cell Biology Fas receptor Kinetics Receptors TNF-Related Apoptosis-Inducing Ligand Gamma Rays biology.protein Cancer research Tetradecanoylphorbol Acetate Camptothecin Tumor necrosis factor alpha Apoptosis Regulatory Proteins Carrier Proteins |
| Zdroj: | Journal of Biological Chemistry. 277:3776-3783 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m107218200 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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