title: Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins.
abstract: 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.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Lianhua
authors.initials: L
authors.lastname: Piao
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakakido
authors.affiliation: Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Japan.
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.|Division of Molecular Modification and Cancer Biology, National Cancer Center, Chuo-ku, Tokyo 104-0045, Japan.
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hamamoto
mesh_terms: D019175:DNA Methylation / Q000502:physiology*; D057809:HEK293 Cells; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D013379:Substrate Specificity / Q000502:physiology
chemical_list: D011495:Histone-Lysine N-Methyltransferase; C515701:SUV39H2 protein, human; D008239:Lysine
keywords: SET domain; SUV39H2; automethylation; oncogene