ASPP1 and ASPP2: Common activators of p53 family members
ASPP1 and ASPP2: Common activators of p53 family members
复制标题
DOI：
10.1128/mcb.24.3.1341-1350.2004
复制
发表时间：
2004-02-01
影响因子：
5.3
通讯作者：
Lu, X
中科院分区：
文献类型：
--
作者：
Bergamaschi, D;Samuels, Y;Lu, X
我们最近发现ASPP 1和ASPP 2刺激p53的凋亡功能。我们在这里表明，ASPP 1和ASPP 2也诱导细胞凋亡独立于p53。通过在体外和体内与p63和p73结合，ASPP 1和ASPP 2刺激p63和p73在Bax、PIG 3和PSMA启动子上的反式激活功能，但不刺激mdm 2或p21（WAF-1/CIP 1）。ASPP 1和ASPP 2的表达还通过选择性诱导内源性p53靶基因（如PIG 3和PIGA，但不诱导mdm 2或p21（WAF-1/CIP 1））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证明（16）ASPP 1和ASPP 2的p53非依赖性凋亡功能主要由p63和p73介导。因此，ASPP 1和ASPP 2是所有p53家族成员的前两个确定的共同激活剂。所有这些结果表明，ASPP 1和ASPP 2可以抑制肿瘤生长，即使在表达突变型p53的肿瘤中。
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.