Acetylation dependent translocation of EWSR1 regulates CHK2 alternative splicing in response to DNA damage
Acetylation dependent translocation of EWSR1 regulates CHK2 alternative splicing in response to DNA damage
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EWSR1 的乙酰化依赖性易位调节 CHK2 选择性剪接以响应 DNA 损伤
DOI：
10.1038/s41388-022-02383-x
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发表时间：
2022-06
期刊：
影响因子：
8
通讯作者：
Jianyuan Luo
中科院分区：
文献类型：
--
作者：
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
尤文肉瘤断点区1（EWSR 1）是FET（FUS/EWSR 1/TAF 15）RNA结合蛋白家族的成员。尤文肉瘤癌蛋白EWS-FLI 1已被广泛研究，而对EWSR 1本身，特别是EWSR 1在响应DNA损伤中的潜在作用知之甚少。在这里，我们发现，紫外线照射诱导乙酰化的EWSR 1，这是必需的核仁易位。我们确定K423、K432、K438、K640和K643为主要的乙酰化位点，p300/CBP和HDAC 3/HDAC 10分别为主要的乙酰转移酶和脱乙酰酶。在机械上，UV诱导的EWSR 1乙酰化抑制了其与剪接体组分U1 C的相互作用，这导致CHK 2的异常剪接，抑制CHK 2对UV照射的反应。综上所述，我们的研究结果揭示了乙酰化作为EWSR 1的一种新的调节修饰，并且对于其在DNA损伤反应中的功能至关重要。
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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DOI：
10.1042/bj20082097
发表时间：
2009-03
期刊：
The Biochemical journal
影响因子：
--
作者：
Iva Klevernic;Simon Morton;R. Davis;P. Cohen
通讯作者：
Iva Klevernic;Simon Morton;R. Davis;P. Cohen
影响因子：
14.9
作者：
Alex D;Lee KA
通讯作者：
Lee KA
DOI：
10.1016/j.bbamcr.2010.01.005
发表时间：
2010-03-01
影响因子：
5.1
作者：
Berge, Elisabet Ognedal;Staalesen, Vidar;Lonning, Per Eystein
通讯作者：
Lonning, Per Eystein
影响因子：
16.8
作者：
Dutertre, Martin;Sanchez, Gabriel;Auboeuf, Didier
通讯作者：
Auboeuf, Didier
影响因子：
13.6
作者：
Han C;Khodadadi-Jamayran A;Lorch AH;Jin Q;Serafin V;Zhu P;Politanska Y;Sun L;Gutierrez-Diaz BT;Pryzhkova MV;Abdala-Valencia H;Bartom ET;Buldini B;Basso G;Velu SE;Sarma K;Mattamana BB;Cho BK;Obeng RC;Goo YA;Jordan PW;Tsirigos A;Zhou Y;Ntziachristos P
通讯作者：
Ntziachristos P