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, ind uce activation of c-Jun N-terminal kinases, We describe here that IL-2 depr ivation-induced apoptosis in TS1 alpha beta cells does not modify c-Jun pro tein levels and correlates Bcl-2 downregulation and an increase in JNK1, bu t not JNK2, activity directly related to the induction of apoptosis. Indeed , downregulation of JNK1 expression using antisense oligonucleotides inhibi ts apoptosis induced by IL-2 withdrawal. Overexpression of Bcl-2 promotes c ell survival and blocks JNK1 activation as well as apoptosis caused by IL-2 deprivation, This suggests that inhibition of the JNK1 signaling pathway m ay be a mechanism through which Bcl-2 promotes cell survival and prevents a poptosis triggered by growth factor withdrawal.