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8-Oxoguanine DNA glycosylase 1 selectively modulates ROS-responsive NF-κB targets through recruitment of MSK1 and phosphorylation of RelA/p65 at Ser276.
Xue, Yaoyao; Li, Chunshuang; Deng, Shihua; Chen, Xin; Han, Jinling; Zheng, Xu; Tian, Miaomiao; Hao, Wenjing; Pan, Lang; Boldogh, Istvan; Ba, Xueqing; Wang, Ruoxi.
Afiliación
  • Xue Y; Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, Jilin, China; College of Life Sciences, Northeast Normal University, Changchun, Jilin, China.
  • Li C; Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, Jilin, China; College of Life Sciences, Northeast Normal University, Changchun, Jilin, China.
  • Deng S; Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, Jilin, China; College of Life Sciences, Northeast Normal University, Changchun, Jilin, China.
  • Chen X; Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, Jilin, China; College of Life Sciences, Northeast Normal University, Changchun, Jilin, China.
  • Han J; Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, Jilin, China; College of Life Sciences, Northeast Normal University, Changchun, Jilin, China.
  • Zheng X; Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, Jilin, China; College of Life Sciences, Northeast Normal University, Changchun, Jilin, China.
  • Tian M; Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, Jilin, China; College of Life Sciences, Northeast Normal University, Changchun, Jilin, China.
  • Hao W; Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
  • Pan L; Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, USA.
  • Boldogh I; Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, USA.
  • Ba X; Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, Jilin, China; College of Life Sciences, Northeast Normal University, Changchun, Jilin, China. Electronic address: baxq755@nenu.edu.cn.
  • Wang R; Institute of Biomedical Sciences, College of Life Sciences, Key Laboratory of Animal Resistance Biology of Shandong Province, Shandong Normal University, Jinan, Shandong, China. Electronic address: wangruoxi@sdnu.edu.cn.
J Biol Chem ; 299(11): 105308, 2023 11.
Article en En | MEDLINE | ID: mdl-37778730
Nuclear factor kappa B (NF-κB) activity is regulated by various posttranslational modifications, of which Ser276 phosphorylation of RelA/p65 is particularly impacted by reactive oxygen species (ROS). This modification is responsible for selective upregulation of a subset of NF-κB targets; however, the precise mechanism remains elusive. ROS have the ability to modify cellular molecules including DNA. One of the most common oxidation products is 8-oxo-7,8-dihydroguanine (8-oxoGua), which is repaired by the 8-oxoguanine DNA glycosylase1 (OGG1)-initiated base excision repair pathway. Recently, a new function of OGG1 has been uncovered. OGG1 binds to 8-oxoGua, facilitating the occupancy of NF-κB at promoters and enhancing transcription of pro-inflammatory cytokines and chemokines. In the present study, we demonstrated that an interaction between DNA-bound OGG1 and mitogen-and stress-activated kinase 1 is crucial for RelA/p65 Ser276 phosphorylation. ROS scavenging or OGG1 depletion/inhibition hindered the interaction between mitogen-and stress-activated kinase 1 and RelA/p65, thereby decreasing the level of phospho-Ser276 and leading to significantly lowered expression of ROS-responsive cytokine/chemokine genes, but not that of Nfkbis. Blockade of OGG1 binding to DNA also prevented promoter recruitment of RelA/p65, Pol II, and p-RNAP II in a gene-specific manner. Collectively, the data presented offer new insights into how ROS signaling dictates NF-κB phosphorylation codes and how the promoter-situated substrate-bound OGG1 is exploited by aerobic mammalian cells for timely transcriptional activation of ROS-responsive genes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: FN-kappa B / ADN Glicosilasas Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: FN-kappa B / ADN Glicosilasas Límite: Animals / Humans Idioma: En Revista: J Biol Chem Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos