Qiu S, Cai Y, Gao X, Gu SZ, Liu ZJ
One of the most important tumor suppression functions of p53 is its ability to induce apoptosis. iASPP is an inhibitory member of the ASPP protein family. It can specifically inhibit the normal function of p53 as a suppressor. The mechanism of iASPP suppressing the cell apoptotosis is through inhibiting the transactivation function of p53 on the promoters of proapoptotic genes by binding with p53. Therefore, relieving the combination of iASPP with p53 and leaving p53 free may be a useful strategy to activate p53 function. We therefore use A34, a small peptide derived from p53 linker region, to investigate the possibility of resuming the apoptosis activity of p53 by sequestering iASPP with p53 and derepressing p53. The results show that A34 can competitively combine with iASPP and therefore release p53 from iASPP; A34 can enhance the transcriptional activity of p53 on the promoters of Bax and PUMA; A34 can increase cell apoptosis and slow tumor growth in vitro and vivo. This study will open the way for using small molecule peptides that directly disturb the interaction of p53 with iASPP, thereby resume function of p53 as a suppressor.