Cross talk between cell death and cell cycle progression: BCL-2 regulates NFAT-mediated activation

Abstract

BCL-2-deficient T cells demonstrate accelerated cell cycle progression and increased apoptosis following activation. Increasing the levels of BCL-2 retarded the G0 → S transition, sustained the levels of cyclin-dependent kinase inhibitor p27(Kip1), and repressed postactivation death. Proximal signal transduction events and immediate early gene transcription were unaffected. However, the transcription and synthesis of interleukin 2 and other delayed early cytokines were markedly attenuated by BCL-2. In contrast, a cysteine protease inhibitor that also blocks apoptosis had no substantial affect upon cytokine production. Interleukin 2 expression requires several transcription factors of which nuclear translocation of NEAT (nuclear factor of activated T cells) and NEAT-mediated transactivation were impaired by BCL- 2. Thus, select genetic aberrations in the apoptotic pathway reveal a cell autonomous coregulation of activation.