Hdmx protein stability is regulated by the ubiquitin ligase activity of Mdm2
Hdmx protein stability is regulated by the ubiquitin ligase activity of Mdm2
复制标题
DOI：
10.1074/jbc.m213034200
复制
发表时间：
2003-10-03
影响因子：
4.8
通讯作者：
Jochemsen, AG
中科院分区：
文献类型：
--
作者：
de Graaf, P;Little, NA;Jochemsen, AG
p53肿瘤抑制蛋白的稳定性受Hdm 2和Hdmx蛋白的关键调节。Hdm 2蛋白水平通过Hdm 2的自身泛素化活性自动调节，并且在转录水平上通过hdm 2基因的p53激活的转录自动调节。除了观察到Mdmx蛋白可以以p53诱导的方式被胱天蛋白酶-3切割之外，对Hdmx表达水平的调节知之甚少。在两个突变体Hdmx蛋白的功能分析中，两个选择性剪接的mRNA的产物，发现Hdmx蛋白是Mdm 2泛素化的靶。Hdmx蛋白的稳定性部分取决于其内部酸性结构域的存在。Mdm 2似乎只需要一个完整的RING结构域就能泛素化Hdmx并靶向其进行蛋白酶体降解。这些发现突出了p53、Mdm 2和Hdmx之间错综复杂的功能关系。
The stability of the p53 tumor suppressor protein is critically regulated by the Hdm2 and Hdmx proteins. Hdm2 protein levels are auto-regulated by the self-ubiquitination activity of Hdm2 and on the transcriptional level by p53-activated transcription of the hdm2 gene. Little is known about the regulation of Hdmx expression levels, apart from the observation that the Mdmx protein can be cleaved by caspase-3 in a p53-inducible manner. In the functional analysis of two mutant Hdmx proteins, products of two alternatively spliced mRNAs, it was found that Hdmx proteins are targets for ubiquitination by Mdm2. The stability of the Hdmx protein is partly dependent on the presence of its internal acidic domain. Mdm2 appears only to require an intact RING domain to be able to ubiquitinate Hdmx and target it for proteasomal degradation. These findings highlight the intricate functional relationships between p53, Mdm2, and Hdmx.