TRANSCRIPTIONAL ACTIVATION PLAYS A ROLE IN THE INDUCTION OF APOPTOSISBY TRANSIENTLY TRANSFECTED WILD-TYPE P53

The p53 tumor suppressor gene has been implicated in the induction of apoptosis in several cell systems, We have recently reported that tran siently-transfected wt p53 is capable of inducing apoptosis in certain transformed cell lines, We demonstrated by quantitative analysis usin g flow cytometry that apoptosis was restricted to the population expre ssing wt, but not mutant, p53, In the present study we use this model system to analyse the functional domains of p53 in the induction of ap optosis, Several constructs expressing mutations or deletions in the C -terminal oligomerization domain, the N-terminal transactivation domai n or the central DNA-binding domain were introduced into HeLa cells, a nd the ability of the expressed proteins to induce apoptosis was evalu ated, All the functional domains were found to be necessary for the in duction of apoptosis, In addition, cycloheximide and actinomycin D inh ibited wt p53-induced apoptosis, We therefore conclude that p53 acts i n this cell system, at least in part, as a transcriptional activator i n the induction of apoptosis.