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

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...

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Main Authors: Piao, Lianhua, Nakakido, Makoto, Suzuki, Takehiro, Dohmae, Naoshi, Nakamura, Yusuke, Hamamoto, Ryuji
Format: Online
Language:English
Published: Impact Journals LLC 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008405/
id pubmed-5008405
recordtype oai_dc
spelling pubmed-50084052016-09-12 Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins Piao, Lianhua Nakakido, Makoto Suzuki, Takehiro Dohmae, Naoshi Nakamura, Yusuke Hamamoto, Ryuji Research Paper 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. Impact Journals LLC 2016-03-14 /pmc/articles/PMC5008405/ /pubmed/26988914 http://dx.doi.org/10.18632/oncotarget.8072 Text en Copyright: © 2016 Piao et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Piao, Lianhua
Nakakido, Makoto
Suzuki, Takehiro
Dohmae, Naoshi
Nakamura, Yusuke
Hamamoto, Ryuji
spellingShingle Piao, Lianhua
Nakakido, Makoto
Suzuki, Takehiro
Dohmae, Naoshi
Nakamura, Yusuke
Hamamoto, Ryuji
Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins
author_facet Piao, Lianhua
Nakakido, Makoto
Suzuki, Takehiro
Dohmae, Naoshi
Nakamura, Yusuke
Hamamoto, Ryuji
author_sort Piao, Lianhua
title Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins
title_short Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins
title_full Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins
title_fullStr Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins
title_full_unstemmed Automethylation of SUV39H2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins
title_sort automethylation of suv39h2, an oncogenic histone lysine methyltransferase, regulates its binding affinity to substrate proteins
description 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.
publisher Impact Journals LLC
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008405/
_version_ 1613641428334804992

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