IL-2 deprivation triggers apoptosis which is mediated by c-Jun N-terminal kinase 1 activation and prevented by Bcl-2.
A variety of environmental stresses, as well as inflammatory cytokines, induce activation of c-Jun N-terminal kinases. We describe here that IL-2 deprivation-induced apoptosis in TS1alphabeta cells does not modify c-Jun protein levels and correlates Bcl-2 downregulation and an increase in JNK1, but not JNK2, activity directly related to the induction of apoptosis. Indeed, downregulation of JNK1 expression using antisense oligonucleotides inhibits apoptosis induced by IL-2 withdrawal. Overexpression of Bcl-2 promotes cell survival and blocks JNK1 activation as well as apoptosis caused by IL-2 deprivation. This suggests that inhibition of the JNK1 signaling pathway may be a mechanism through which Bcl-2 promotes cell survival and prevents apoptosis triggered by growth factor withdrawal.
Cerezo
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Department of Immunology and Oncology, Centro Nacional de Biotecnología, Universidad Autónoma, Campus de Cantoblanco, E-28049 Madrid, Spain.
Martínez-A
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C
González
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Gómez
J
J
Rebollo
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D000818:Animals; D017209:Apoptosis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation; D004789:Enzyme Activation; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D007376:Interleukin-2 / Q000172:deficiency*; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*
D007376:Interleukin-2; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D011494:Protein Kinases; D048056:Mitogen-Activated Protein Kinase 9; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases