Research Papers:

PRMT6 increases cytoplasmic localization of p21CDKN1A in cancer cells through arginine methylation and makes more resistant to cytotoxic agents

Makoto Nakakido, Zhenzhong Deng, Takehiro Suzuki, Naoshi Dohmae, Yusuke Nakamura and Ryuji Hamamoto _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2015; 6:30957-30967. https://doi.org/10.18632/oncotarget.5143

Metrics: PDF 1047 views  |   HTML 1381 views  |   ?  


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

Correspondence to:

Ryuji Hamamoto, e-mail: rhamamoto@medicine.bsd.uchicago.edu

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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 5143