ASPP1和ASPP2：p53家族成员的常见激活剂。
ASPP1 and ASPP2: common activators of p53 family members.
作者信息
Bergamaschi Daniele, Samuels Yardena, Jin Boquan, Duraisingham Sai, Crook Tim, Lu Xin
机构信息
Ludwig Institute for Cancer Research, Imperial College School of Medicine, St. Mary's Campus, London W2 1PG, United Kingdom.
出版信息
Mol Cell Biol. 2004 Feb;24(3):1341-50. doi: 10.1128/MCB.24.3.1341-1350.2004.
We recently showed that ASPP1 and ASPP2 stimulate the apoptotic function of p53. We show here that ASPP1 and ASPP2 also induce apoptosis independently of p53. By binding to p63 and p73 in vitro and in vivo, ASPP1 and ASPP2 stimulate the transactivation function of p63 and p73 on the promoters of Bax, PIG3, and PUMA but not mdm2 or p21(WAF-1/CIP1). The expression of ASPP1 and ASPP2 also enhances the apoptotic function of p63 and p73 by selectively inducing the expression of endogenous p53 target genes, such as PIG3 and PUMA, but not mdm2 or p21(WAF-1/CIP1). Removal of endogenous p63 or p73 with RNA interference demonstrated that (16) the p53-independent apoptotic function of ASPP1 and ASPP2 is mediated mainly by p63 and p73. Hence, ASPP1 and ASPP2 are the first two identified common activators of all p53 family members. All these results suggest that ASPP1 and ASPP2 could suppress tumor growth even in tumors expressing mutant p53.
我们最近发现ASPP1和ASPP2可刺激p53的凋亡功能。我们在此表明，ASPP1和ASPP2也能独立于p53诱导细胞凋亡。通过在体外和体内与p63和p73结合，ASPP1和ASPP2刺激p63和p73对Bax、PIG3和PUMA启动子的反式激活功能，但不刺激mdm2或p21（WAF-1/CIP1）的反式激活功能。ASPP1和ASPP2的表达还通过选择性诱导内源性p53靶基因（如PIG3和PUMA，但不包括mdm2或p21（WAF-1/CIP1））的表达来增强p63和p73的凋亡功能。用RNA干扰去除内源性p63或p73表明，（16）ASPP1和ASPP2不依赖p53的凋亡功能主要由p63和p73介导。因此，ASPP1和ASPP2是最早被鉴定出的所有p53家族成员的共同激活因子。所有这些结果表明，即使在表达突变p53的肿瘤中，ASPP1和ASPP2也可能抑制肿瘤生长。
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