Acetylation Dependent Translocation of EWSR1 Regulates CHK2 Alternative Splicing in Response to DNA Damage

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2022 Jun 22

PMID 35732801

Authors

Tianzhuo Zhang

Zhe Wang

Minghui Liu

Lu Liu

Xin Yang

Yu Zhang

Juntao Bie

Yutong Li

Mengmeng Ren

Chen Song

Wengong Wang

Hongyu Tan

Jianyuan Luo

Affiliations

Soon will be listed here.

Abstract

Ewing sarcoma breakpoint region 1 (EWSR1) is a member of FET (FUS/EWSR1/TAF15) RNA-binding family of proteins. The Ewing sarcoma oncoprotein EWS-FLI1 has been extensively studied, while much less is known about EWSR1 itself, especially the potential role of EWSR1 in response to DNA damage. Here, we found that UV irradiation induces acetylation of EWSR1, which is required for its nucleoli translocation. We identified K423, K432, K438, K640, and K643 as the major acetylation sites, p300/CBP and HDAC3/HDAC10 as the major acetyltransferases and deacetylases, respectively. Mechanically, UV-induced EWSR1 acetylation repressed its interaction with spliceosomal component U1C, which caused abnormal splicing of CHK2, suppressing the activity of CHK2 in response to UV irradiation. Taken together, our findings uncover acetylation as a novel regulatory modification of EWSR1, and is essential for its function in DNA damage response.

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