MDMX inhibits the p300/CBP-mediated acetylation of p53
MDMX inhibits the p300/CBP-mediated acetylation of p53
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DOI：
10.1089/104454902320219077
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发表时间：
2002-07-01
影响因子：
3.1
通讯作者：
McCormick, F
中科院分区：
文献类型：
--
作者：
Sabbatini, P;McCormick, F
P300/CBP介导的P53乙酰化显著增强P53介导的反式激活和生长抑制。MDM2通过需要稳定的P53-MDM2相互作用和对脱乙酰酶抑制剂TSA敏感的机制来抑制p300/CBP对P53的乙酰化。MDMX是一种类似MDM2的蛋白，与MDM2具有与P53相互作用的能力，进而抑制P53介导的转录。因此，有兴趣确定MDMX是否也能抑制p300/CBP对P53的乙酰化。我们证明MDMX显著抑制内源性和异位表达的p300/CBP诱导的P53乙酰化。我们还证明了MDMX的P53结合域是MDMX介导的抑制P53乙酰化所必需的。我们的结果表明，MDMX与MDM2一样，具有调节潜在重要的P53翻译后修饰的能力。这些结果可能对MDMX介导的发育过程中P53活性的调节具有重要的生物学意义。
The p300/CBP-mediated acetylation of p53 significantly potentiates p53-mediated transactivation and growth inhibition. MDM2 inhibits the acetylation of p53 by p300/CBP through a mechanism that requires a stable p53-MDM2 interaction and that is sensitive to the deacetylase inhibitor, TSA. MDMX is an MDM2-like protein that shares with MDM2 the ability to interact with p53 and, in turn, inhibit p53-mediated transcription. It was therefore of interest to determine if MDMX could also inhibit the acetylation of p53 by p300/CBP. We demonstrate that MDMX dramatically inhibits the acetylation of p53 induced by both endogenous and ectopically expressed p300/CBP. We also demonstrate that the p53-binding domain of MDMX is required for the MDMX-mediated inhibition of p53 acetylation. Our results indicate that MDMX shares with MDM2 the ability to regulate a potentially important post-translational modification of p53. These results may have important biologic implications with respect to the MDMX-mediated regulation of p53 activity during development.