The Beatson Institute for Cancer Research; Glasgow, UK.
Cell Cycle. 2011 Sep 15;10(18):3176-88. doi: 10.4161/cc.10.18.17436.
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.
肿瘤抑制因子 p53 广泛受到翻译后修饰的调控，包括被小泛素相关修饰物 SUMO 修饰。我们在此表明，先前显示能促进 p53 的泛素化、Nedd8 化和 SUMO-1 化的 MDM2，还能增强内源性 SUMO-2/3 与 p53 的连接。Sumoylation 活性需要 p53-MDM2 结合，但不依赖于完整的 RING 指。ARF 和 L11 都能促进 p53 的 SUMO-2/3 连接。然而，与先前描述的由 MDM2-ARF 复合物介导的 p53 的 SUMO-1 连接不同，这种活性不依赖于 MDM2 重新定位到核仁的能力。有趣的是，SUMO 共有序列在小鼠 p53 中并不保守，因此它不被 SUMO-2/3 修饰。最后，我们表明 SUMO-2/3 与 p53 的连接与一组 p53 靶基因的激活和抑制的减少相关。
