PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53.
PHF20 is an effector protein of p53 double lysine methylation that stabilizes and activates p53.
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DOI：
10.1038/nsmb.2353
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发表时间：
2012-09
影响因子：
16.8
通讯作者：
Mer, Georges
中科院分区：
文献类型：
--
作者：
Cui, Gaofeng;Park, Sungman;Badeaux, Aimee I.;Kim, Donghwa;Lee, Joseph;Thompson, James R.;Yan, Fei;Kaneko, Satoshi;Yuan, Zengqiang;Botuyan, Maria Victoria;Bedford, Mark T.;Cheng, Jin Q.;Mer, Georges
PHF20是一种多结构域蛋白，是赖氨酸乙酰转移酶复合物的亚基，可使组蛋白H4和p53乙酰化，但其功能尚不清楚。通过生化、生物物理和细胞方法，我们确定PHF20是p53的直接调节剂。PHF20中的Tudor结构域识别了p53在Lys370或Lys382位点的二甲基化，并且该Tudor结构域的同二聚体形式可以与p53上的两个二甲基化位点以增强的亲和力结合，表明多价相互作用。与PHF20的关联通过减少mdm2介导的p53泛素化和降解来促进p53的稳定和激活。PHF20有助于p53在DNA损伤时的上调，PHF20在不同细胞系中的异位表达导致表型变化，这是p53激活的标志。总的来说，我们的工作确定了PHF20作为p53甲基化的效应物，稳定和激活p53。
PHF20 is a multidomain protein and subunit of a lysine acetyltransferase complex that acetylates histone H4 and p53 but whose function is unclear. Using biochemical, biophysical and cellular approaches, we determined that PHF20 is a direct regulator of p53. A Tudor domain in PHF20 recognized p53 dimethylated at Lys370 or Lys382 and a homodimeric form of this Tudor domain could associate with the two dimethylated sites on p53 with enhanced affinity, indicating a multivalent interaction. Association with PHF20 promotes stabilization and activation of p53 by diminishing Mdm2-mediated p53 ubiquitylation and degradation. PHF20 contributes to upregulation of p53 in response to DNA damage, and ectopic expression of PHF20 in different cell lines leads to phenotypic changes that are hallmarks of p53 activation. Overall our work establishes that PHF20 functions as an effector of p53 methylation that stabilizes and activates p53.
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