Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins
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Lianhua Piao1, Makoto Nakakido1, Takehiro Suzuki2, Naoshi Dohmae2, Yusuke Nakamura1, Ryuji Hamamoto1,3
1Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA
2Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan
3Division of Molecular Modification and Cancer Biology, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan
Ryuji Hamamoto, e-mail: [email protected]
Keywords: SUV39H2, oncogene, automethylation, SET domain
Received: November 12, 2015 Accepted: February 25, 2016 Published: March 14, 2016
We previously reported that the histone lysine methyltransferase SUV39H2, which is overexpressed in various types of human cancer, plays a critical role in the DNA repair after double strand breakage, and possesses oncogenic activity. Although its biological significance in tumorigenesis has been elucidated, the regulatory mechanism of SUV39H2 activity through post-translational modification is not well known. In this study, we demonstrate in vitro and in vivo automethylation of SUV39H2 at lysine 392. Automethylation of SUV39H2 led to impairment of its binding affinity to substrate proteins such as histone H3 and LSD1. Furthermore, we observed that hyper-automethylated SUV39H2 reduced methylation activities to substrates through affecting the binding affinity to substrate proteins. Our finding unveils a novel autoregulatory mechanism of SUV39H2 through lysine automethylation.
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