PRMT6 increases cytoplasmic localization of p21CDKN1A in cancer cells through arginine methylation and makes more resistant to cytotoxic agents
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Makoto Nakakido1,*, Zhenzhong Deng1,*, Takehiro Suzuki2, Naoshi Dohmae2, Yusuke Nakamura1, Ryuji Hamamoto1
1Section of Hematology/Oncology, Department of Medicine, The University of Chicago, MC2115, Chicago, IL 60637, USA
2Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Saitama 351–0198, Japan
*These authors have contributed equally to this work
Ryuji Hamamoto, e-mail: firstname.lastname@example.org
Keywords: p21CDKN1A, arginine methylation, PRMT6, subcellular localization, cancer chemoresistance
Received: July 08, 2015 Accepted: August 12, 2015 Published: September 03, 2015
p21CDKN1A 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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