Arginine methylation regulates the p53 response
Arginine methylation regulates the p53 response
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DOI：
10.1038/ncb1802
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发表时间：
2008-12-01
影响因子：
21.3
通讯作者：
La Thangue, Nicholas B.
中科院分区：
文献类型：
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作者：
Jansson, Martin;Durant, Stephen T.;La Thangue, Nicholas B.
p53肿瘤抑制蛋白对DNA损伤的响应激活导致细胞凋亡或细胞周期停滞。酶修饰被广泛认为影响和调节p53活性。我们在这里描述了一个水平的翻译后控制，有一个重要的功能后果的p53反应。我们表明，蛋白质精氨酸甲基转移酶（PRMT）5，作为一个辅助因子的DNA损伤响应辅激活复合物，与p53相互作用，是负责甲基化p53。精氨酸甲基化在p53应答过程中受到调节，并影响p53的靶基因特异性。此外，PRMT5耗竭触发p53依赖性细胞凋亡。因此，精氨酸残基上的甲基化是p53反应期间的潜在控制机制。
Activation of the p53 tumour suppressor protein in response to DNA damage leads to apoptosis or cell-cycle arrest. Enzymatic modifications are widely believed to affect and regulate p53 activity. We describe here a level of post-translational control that has an important functional consequence on the p53 response. We show that the protein arginine methyltransferase (PRMT) 5, as a co-factor in a DNA damage responsive co-activator complex that interacts with p53, is responsible for methylating p53. Arginine methylation is regulated during the p53 response and affects the target gene specificity of p53. Furthermore, PRMT5 depletion triggers p53-dependent apoptosis. Thus, methylation on arginine residues is an underlying mechanism of control during the p53 response.