p53 suppresses the activation of the Bcl-2 promoter by the Brn-3a POU family transcription factor

The Brn-3a POU family transcription factor has been shown to strongly activ ate expression of the Bcl-2 protooncogene and thereby protect neuronal cell s from programmed cell death (apoptosis), This activation of the Bcl-2 prom oter by Brn-3a is strongly inhibited by the p53 anti-oncogene protein. This inhibitory effect of p53 on Brn-3a-mediated transactivation is observed wi th nonoverlapping gene fragments containing either the Bcl-2 pi or p2 promo ters but is not observed with other Brn-3a-activated promoters such as in t he gene encoding alpha-internexin or with an isolated Bm-Sa binding site fr om the Bcl-2 promoter linked to a heterologous promoter. In contrast, p53 m utants, which are incapable of binding to DNA, do not affect Brn-3a-mediate d activation of the Bcl-2 pi and p2 promoters. Moreover, Brn-3a and p53 hav e been shown to bind to adjacent sites in the p2 promoter and to directly i nteract with one another, both in vitro and in vivo, with this interaction being mediated by the POU domain of Brn-3a and the DNA binding domain of p5 3, The significance of these effects is discussed in terms of the antagonis tic effects of Bcl-2 and p53 on the rate of apoptosis and the overexpressio n of Brn-3a in specific tumor cell types.