Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins

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 el...

Full description

Saved in:
Bibliographic Details
Published in:Oncotarget 2016-04, Vol.7 (16), p.22846-22856
Main Authors: Piao, Lianhua, Nakakido, Makoto, Suzuki, Takehiro, Dohmae, Naoshi, Nakamura, Yusuke, Hamamoto, Ryuji
Format: Article
Language:English
Subjects:
DNA Methylation - physiology
HEK293 Cells
Histone-Lysine N-Methyltransferase - chemistry
Histone-Lysine N-Methyltransferase - metabolism
Humans
Lysine - chemistry
Lysine - metabolism
Protein Binding
Protein Processing, Post-Translational
Research Paper
Substrate Specificity - physiology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.8072