MDM2 promotes SUMO-2/3 modification of p53 to modulate transcriptional activity
MDM2 promotes SUMO-2/3 modification of p53 to modulate transcriptional activity
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DOI：
10.4161/cc.10.18.17436
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发表时间：
2011-09
期刊：
影响因子：
4.3
通讯作者：
M. Stindt;S. Carter;Arnaud M. Vigneron;K. Ryan;K. Vousden
中科院分区：
文献类型：
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作者：
M. Stindt;S. Carter;Arnaud M. Vigneron;K. Ryan;K. Vousden
肿瘤抑制因子 p53 受到翻译后修饰的广泛调节，包括小泛素相关修饰剂 SUMO 的修饰。我们在此表明，MDM2（之前已证明可促进 p53 的泛素、Nedd8 和 SUMO-1 修饰）也可以增强内源 SUMO-2/3 与 p53 的缀合。 Sumoylation 活性需要 p53-MDM2 结合，但不依赖于完整的 RING 指。 ARF和L11均可促进p53的SUMO-2/3缀合。然而，与之前描述的 MDM2-ARF 复合物对 p53 的 SUMO-1 缀合不同，这种活性不依赖于 MDM2 重新定位到核仁的能力。有趣的是，SUMO 共识在小鼠 p53 中并不保守，因此不会被 SUMO-2/3 修改。最后，我们表明 SUMO-2/3 与 p53 的缀合与 p53 靶基因子集的激活和抑制的减少相关。
The tumor suppressor p53 is extensively regulated by post-translational modification, including modification by the small ubiquitin-related modifier SUMO. We show here that MDM2, previously shown to promote ubiquitin, Nedd8 and SUMO-1 modification of p53, can also enhance conjugation of endogenous SUMO-2/3 to p53. Sumoylation activity requires p53-MDM2 binding but does not depend on an intact RING finger. Both ARF and L11 can promote SUMO-2/3 conjugation of p53. However, unlike the previously described SUMO-1 conjugation of p53 by an MDM2-ARF complex, this activity does not depend on the ability of MDM2 to relocalize to the nucleolus. Interestingly, the SUMO consensus is not conserved in mouse p53, which is therefore not modified by SUMO-2/3. Finally, we show that conjugation of SUMO-2/3 to p53 correlates with a reduction of both activation and repression of a subset of p53-target genes.