ESSENTIAL ROLE FOR P53-MEDIATED TRANSCRIPTION IN E1A-INDUCED APOPTOSIS

Baby rat kidney (BRK) cell lines transformed by E1A and a temperature- sensitive p53 [tsp53(val135)] undergo rapid apoptosis when p53 assumes the wild-type conformation at the permissive temperature. Wild-type p 53 function is therefore required for induction of apoptosis in respon se to growth deregulation by E1A. BRK cells transformed by E1A and a t ranscriptionally defective temperature-sensitive p53 [tsp53(22-23val13 5)] are dramatically impaired for the ability to mediate E1A-induced a poptosis at the permissive temperature. The tsp53(22-23val135), howeve r, still retains some ability to suppress cell growth. Thus, the activ ity of p53 as a transcription factor is directly correlated with the a bility of E1A to induce apoptosis. In addition, there may exist at lea st two different mechanisms by which p53 can suppress cell-cycle progr ession, only one of which is dependent on p53-mediated transcription.