Abstract
Bclโ2 family proteins play central roles in the regulation of most, if not all, apoptotic pathways, and hence this family plays a critical role in oncogenesis. The Bclโ2 homology 3 (BH3)โonly members of this family are โproapoptotic,โ promoting apoptosis by sensing cellular stresses: that is, they are activated or induced in response to stress stimuli. These BH3โonly proteins then interfere with the function of โprosurvivalโ Bclโ2 family members, thereby promoting the progression of apoptosis. It has long been recognized that the induction and activation of each of the BH3โonly proteins are subject to the type of stress stimulus. Although it was originally assumed that all the BH3โonly proteins exert similar effects on the downstream apoptotic machinery, recent studies have uncovered their distinct functional properties, indicating the operation of more intricate, versatile control mechanisms of apoptosis. In this review, we will summarize recent findings on the diversity in the activation and function of BH3โonly proteins. In particular, we focus on the overlapping and individual roles of 2 BH3โonly proteins, Puma and Noxa, in the context of the apoptotic response induced by the tumor suppressor p53. ยฉ 2006 WileyโLiss, Inc.