RING domain-mediated interaction is a requirement for MDM2's E3 ligase activity
RING domain-mediated interaction is a requirement for MDM2's E3 ligase activity
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DOI：
10.1158/0008-5472.can-07-1313
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发表时间：
2007-07-01
期刊：
影响因子：
11.2
通讯作者：
Yuan, Zhi-Min
中科院分区：
文献类型：
--
作者：
Kawai, Hidehiko;Lopez-Pajares, Vanessa;Yuan, Zhi-Min
MDM2的RING结构域对其E3连接酶活性至关重要，介导其与自身及其结构同源物MDMX的结合。尽管有报道称RING结构域相互作用至关重要，但它们如何影响MDM2的E3连接酶活性尚不清楚。我们报道E3连接酶的活性需要RING结构域依赖性复合物的形成。在体内，MDM2和MDMX杂环复合物是MDM2同环复合物的主要形式。重要的是，MDM2/MDMX异环复合物比MDM2同环复合物表现出更大的E3连接酶活性。破坏MDM2和MDMX之间的结合导致p53的丰度和活性显著增加，强调了这种异复合体在p53控制中的功能重要性。
The RING domain of MDM2 that is essential for its E3 ligase activity mediates binding to itself and its structural homologue MDMX. Whereas it has been reported that RING domain interactions are critical, it is not well understood how they affect the E3 ligase activity of MDM2. We report that the E3 ligase activity requires the RING domain-dependent complex formation. In vivo, MDM2 and MDMX hetero-RING complexes are the predominant form versus the MDM2 homo-RING complex. Importantly, the MDM2/MDMX hetero-RING complexes exhibit a greater E3 ligase activity than the MDM2 homo-RING complexes. Disruption of the binding between MDM2 and MDMX resulted in a marked increase in both abundance and activity of p53, emphasizing the functional importance of this heterocomplex in p53 control.