Differential regulation of cell cycle-related proteins by CD95 engagement in thymocytes and T cell leukemic cell line, Jurkat.
CD95 engagement results in apoptosis in thymocytes and in the Jurkat human leukemic T cell line. Biochemical analyses in CD95-engaged thymocytes and Jurkat cells revealed dysregulation of the G1/S cell cycle control point. Cyclin E was upregulated upon CD95 engagement, suggesting G1-to-S progression, but there was no upregulation of cyclin A. Instead, cyclin E was degraded by caspases. In addition, c-myc that normally acts on S-phase progression through the activation of cdc25A appeared to be involved in the inhibition of S-phase progression after CD95 ligation. This implies that G1-->S progression and apoptosis are intimately linked in cells undergoing CD95 ligation. Furthermore, our data suggest that CD95-induced apoptosis occurs at the G1/S phase transition. We therefore suggest that CD95 engagement not only triggers death signals but also affects the G1/S checkpoint.
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The Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. pshoe@plaza.snu.ac.kr
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D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D061945:Caspase Inhibitors; D018797:Cell Cycle Proteins / Q000235:genetics*; D002469:Cell Separation; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D016193:G1 Phase; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D008808:Mice, Inbred CBA; D016196:S Phase; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism*; D019014:fas Receptor / Q000276:immunology*
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D018797:Cell Cycle Proteins; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D019014:fas Receptor