p53-Dependent apoptosis in the absence of transcriptional activation of p53-target genes

Studies of specific gene induction during apoptosis of cell lines conditionally immortalized by SV40

“…This induction is more rapid than that of mdm-2, in agreement with the pro- Table 1 Expression of genes indentified by their diffential expression during apoptosis Gene(s) Induced in Expression in REtsAF Calmodulin, chondroitin sulfate Glucocorticoids induced thymocyte apoptosis [11,20] Not detected proteoglycan core protein RP8 Glutathione S-transferase Ybl Clusterin Ubiquitin Glucocorticoids or radiation induced thymocyte apoptosis [15] Prostate regression [32] and steroid induced lymphocyte apoptosis [21] Prostate regression and various other cell death process [17] Radiation-induced lymphocyte apoptosis [18] and insect muscles degeneration [19] [29], which suggest that, in some cells, p53 can mediate apoptosis by repressing survival genes. Recently, a reevaluation of the role of de novo protein synthesis in thymocyte apoptosis has also suggested that inhibitors of protein synthesis may delay apoptosis rather than prevent it [30], suggesting that some of the components of the apoptotic machinery are already present before apoptosis induction.…”

Twenty years of p53 research: structural and functional aspects of the p53 protein

“…In some situations, transcriptional activation by p53 is dispensable for the induction of apoptosis, since mutants in p53 which fail to activate transcription can still induce apoptosis (Chen et al, 1996;Haupt et al, 1995a) and p53-dependent apoptosis can occur in the presence of inhibitors of transcriptional and translation (Caelles et al, 1994).…”

Body language: the function of PML nuclear bodies in apoptosis regulation

“…However, p53 can also induce apoptosis via transcription-independent mechanisms and translocation to the mitochondria triggering cytochrome c release and caspase activation. [124][125][126][127] Basically, two mechanistically different pathways mediating p53 activation have been identified. One pathway relies on the activation of a set of protein kinases, which directly phosphorylate serine or threonine residues within the Nterminal transactivation domain and the C-terminal regulatory domain of p53.…”