期刊
ONCOTARGET
卷 6, 期 31, 页码 30957-30967出版社
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.5143
关键词
p21(CDKN1A); arginine methylation; PRMT6; subcellular localization; cancer chemoresistance
p21(CDKN1A) is known as a potent inhibitor of cyclin-dependent kinase (CDK), which regulates cell cycle in response to various stimuli, including DNA damage, on the p53-dependent manner. Here we demonstrate that protein arginine methyltransferase 6 (PRMT6) methylates p21 at arginine 156 and promotes phosphorylation of threonine 145 on p21, resulting in the increase of cytoplasmic localization of p21. The cytoplasmic presence of p21 makes cancer cells more resistant to cytotoxic agents. Our results indicate that PRMT6 appears to be one of the key proteins to dysregulate p21 functions in human cancer, and targeting this pathway may be an appropriate strategy for development of anticancer drugs.
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