iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72 polymorphic p53
iASPP preferentially binds p53 proline-rich region and modulates apoptotic function of codon 72 polymorphic p53
复制标题
DOI：
10.1038/ng1879
复制
发表时间：
2006-10-01
期刊：
影响因子：
30.8
通讯作者：
Lu, Xin
中科院分区：
文献类型：
--
作者：
Bergamaschi, Daniele;Samuels, Yardena;Lu, Xin
iASPP 是进化上最保守的 p53 抑制剂之一，而 ASPP1 和 ASPP2 是 p53 的激活剂。我们在此表明，除了 DNA 结合域之外，ASPP 家族成员还与 p53 富含脯氨酸的区域结合，该区域在密码子 72 处包含最常见的 p53 多态性。此外，ASPP 家族成员，特别是 iASPP，比 p53Arg72 更有效地结合并调节 p53Pro72 的活性。因此，逃避 iASPP 的负调控是一种新发现的机制，通过该机制，p53Arg72 比 p53Pro72 更有效地激活细胞凋亡。
iASPP is one of the most evolutionarily conserved inhibitors of p53, whereas ASPP1 and ASPP2 are activators of p53. We show here that, in addition to the DNA-binding domain, the ASPP family members also bind to the proline-rich region of p53, which contains the most common p53 polymorphism at codon 72. Furthermore, the ASPP family members, particularly iASPP, bind to and regulate the activity of p53Pro72 more efficiently than that of p53Arg72. Hence, escape from negative regulation by iASPP is a newly identified mechanism by which p53Arg72 activates apoptosis more efficiently than p53Pro72.