Critical role for a central part of Mdm2 in the ubiquitylation of p53
Critical role for a central part of Mdm2 in the ubiquitylation of p53
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DOI：
10.1128/mcb.23.14.4929-4938.2003
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发表时间：
2003-07-01
影响因子：
5.3
通讯作者：
Jochemsen, AG
中科院分区：
文献类型：
--
作者：
Meulmeester, E;Frenk, R;Jochemsen, AG
p53蛋白的稳定性受Mdm 2调节。通过作为E3泛素连接酶，Mdm 2指导p53的泛素化及其随后通过26 S蛋白酶体的降解。相比之下，Mdmx蛋白，虽然在结构上类似于Mdm 2，但不能在体内泛素化或降解p53。为了确定哪些结构域决定了Mdm 2和Mdmx之间的这种功能差异，从而对p53泛素化和降解至关重要，我们产生了Mdm 2-Mdmx嵌合构建体。在这里，我们表明，除了一个功能齐全的Mdm 2环指，Mdm 2的内部结构域（残基202至302）是必不可少的p53泛素化。引人注目的是，该结构域的功能可以反式实现，表明RING结构域和该内部区域在p53的泛素化中执行不同的活动。
The stability of the p53 protein is regulated by Mdm2. By acting as an E3 ubiquitin ligase, Mdm2 directs the ubiquitylation of p53 and its subsequent degradation by the 26S proteasome. In contrast, the Mdmx protein, although structurally similar to Mdm2, cannot ubiquitylate or degrade p53 in vivo. To ascertain which domains determine this functional difference between Mdm2 and Mdmx and consequently are essential for p53 ubiquitylation and degradation, we generated Mdm2-Mdmx chimeric constructs. Here we show that, in addition to a fully functional Mdm2 RING finger, an internal domain of Mdm2 (residues 202 to 302) is essential for p53 ubiquitylation. Strikingly, the function of this domain can be fulfilled in trans, indicating that the RING domain and this internal region perform distinct activities in the ubiquitylation of p53.