ASPP proteins specifically stimulate the apoptotic function of p53

We identified a family of proteins termed ASPP. ASPP1 is a protein homologo us to 53BP2, the C-terminal half of ASPP2. ASPP proteins interact with p53 and specifically enhance p53-induced apoptosis but not cell cycle arrest. I nhibition of endogenous ASPP function suppresses the apoptotic function of endogenous p53 in response to apoptotic stimuli. ASPP enhance the DNA bindi ng and transactivation function of p53 on the promoters of proapoptotic gen es in vivo. Two tumor-derived p53 mutants with reduced apoptotic function w ere defective in cooperating with ASPP in apoptosis induction. The expressi on of ASPP is frequently downregulated in human breast carcinomas expressin g wild-type p53 but not mutant p53. Therefore, ASPP regulate the tumor supp ression function of p53 in vivo.