SUMOylation modification of FTO facilitates oxidative damage response of arsenic by IGF2BP3 in an m6A-dependent manner

作者全名：Zhang, Hongyang; Chen, Qian; Han, Huifang; Guo, Changxin; Jiang, Xuejun; Xia, Yinyin; Zhang, Yunxiao; Zhou, Lixiao; Zhang, Jun; Tian, Xin; Mao, Lejiao; Qiu, Jingfu; Zou, Zhen; Chen, Chengzhi

作者地址：[Zhang, Hongyang; Han, Huifang; Guo, Changxin; Qiu, Jingfu] Chongqing Med Univ, Sch Publ Hlth, Dept Hlth Lab Technol, Chongqing 400016, Peoples R China; [Chen, Qian; Xia, Yinyin; Zhang, Yunxiao; Zhou, Lixiao; Chen, Chengzhi] Chongqing Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Chongqing 400016, Peoples R China; [Jiang, Xuejun] Chongqing Med Univ, Ctr Expt Teaching Publ Hlth, Expt Teaching & Management Ctr, Chongqing 400016, Peoples R China; [Zhang, Jun; Mao, Lejiao; Zou, Zhen] Chongqing Med Univ, Sch Lab Med, Mol Biol Lab Resp Dis, Chongqing 400016, Peoples R China; [Zhang, Jun; Qiu, Jingfu; Zou, Zhen; Chen, Chengzhi] Chongqing Med Univ, Res Ctr Environm & Human Hlth, Sch Publ Hlth, Chongqing 400016, Peoples R China; [Tian, Xin] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurol, Chongqing, Peoples R China

通信作者：Chen, CZ (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Chongqing 400016, Peoples R China.; Zou, Z (通讯作者)，Chongqing Med Univ, Sch Lab Med, Mol Biol Lab Resp Dis, Chongqing 400016, Peoples R China.

来源：JOURNAL OF HAZARDOUS MATERIALS

ESI学科分类：ENGINEERING

WOS号：WOS:001239472600001

JCR分区：Q1

影响因子：12.2

年份：2024

卷号：472

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Oxidative damage; m6A; FTO; SUMOylation; Arsenic

摘要：N6-methyladenosine (m6A) is the most common form of internal post -transcriptional methylation observed in eukaryotic mRNAs. The abnormally increased level of m6A within the cells can be catalyzed by specific demethylase fat mass and obesity -associated protein (FTO) and stay in a dynamic and reversible state. However, whether and how FTO regulates oxidative damage via m6A modification remain largely unclear. Herein, by using both in vitro and in vivo models of oxidative damage induced by arsenic, we demonstrated for the first time that exposure to arsenic caused a significant increase in SUMOylation of FTO protein, and FTO SUMOylation at lysine (K)- 216 site promoted the down -regulation of FTO expression in arsenic target organ lung, and therefore, remarkably elevating the oxidative damage via an m6A-dependent pathway by its specific m6A reader insulinlike growth factor -2 mRNA-binding protein -3 (IGF2BP3). Consequently, these findings not only reveal a novel mechanism underlying FTO-mediated oxidative damage from the perspective of m6A, but also imply that regulation of FTO SUMOylation may serve as potential approach for treatment of oxidative damage.

基金机构：Technology Research Program of Chongqing Municipal Education Commission [KJQN 202200448]; Future Medical Youth Innovation Team of Chongqing Medical University [W0043]; Chongqing Post-graduate Research Innovation Project [CYS23356]; Chongqing Medical Scientific Research Project, Joint project of Chongqing Health Com-mission and Science and Technology Bureau [2023DBXM006]

基金资助正文：This research was supported by National Natural Science Foundation of China (Grant Number: 82001378) , Postdoctoral Fellowship Program of China Postdoctoral Science Foundation (GZC20233340) , Natural Science Foundation of Chongqing (cstc2022ycjh-bgzxm0101, cstc2021jcyj-msxmX0141, CSTB2023NSCQ-LZX0059) . Science andTechnology Research Program of Chongqing Municipal Education Commission (KJQN 202200448) . Future Medical Youth Innovation Team of Chongqing Medical University (W0043) . Chongqing Post-graduate Research Innovation Project (CYS23356) . Chongqing Medical Scientific Research Project, Joint project of Chongqing Health Commission and Science and Technology Bureau (2023DBXM006) . J.Z., Z.Z. and C.C were supported by young talent of Bayu scholar.r Technology Research Program of Chongqing Municipal Education Commission (KJQN 202200448) . Future Medical Youth Innovation Team of Chongqing Medical University (W0043) . Chongqing Post-graduate Research Innovation Project (CYS23356) . Chongqing Medical Scientific Research Project, Joint project of Chongqing Health Com-mission and Science and Technology Bureau (2023DBXM006) . J.Z., Z.Z. and C.C were supported by young talent of Bayu scholar.