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Post-translational Modification in Control of SIRT1 Stability during DNA Damage Response
Ouyang, Chenxi1; Lu, Guang1; He, Weifeng2; Bay, Boon Huat3; Shen, Han Ming1,4,5
2022
Source PublicationInternational Journal of Biological Sciences
ISSN1449-2288
Volume18Issue:7Pages:2655-2669
Abstract

SIRT1 (silent mating type information regulation 2 homolog 1), a class III histone deacetylase, is known to participate in multiple steps of the DNA damage response (DDR) by deacetylating several key DDR proteins. At present, the mechanisms regulating SIRT1 protein stability upon DNA damage have yet to be fully elucidated. In this study, we reveal that, under severe DNA damage, SIRT1 undergoes two forms of post-translational modifications (PTMs): (i) increased polyubiquitination and proteasomal degradation mediated by TRIM28 (tripartite motif-containing protein 28), a RING-domain E3 ligase; and (ii) cleavage at C-terminal mediated by caspases. Importantly, there is reciprocal effects between these forms of PTMs: while suppression of proteasome reduces caspases-mediated cleavage, the cleaved SIRT1 has enhanced interaction with TRIM28, thus facilitating the ubiquitination and proteasomal degradation of SIRT1. Functionally, SIRT1 works as an anti-apoptotic protein in DDR, and the above-mentioned PTMs of SIRT1 subsequently enhances cell death induced by DNA damage agents. Thus, our study has uncovered a pivotal role of SIRT1 post-translational regulation in determining cell fate in DDR.

KeywordCaspases Cleavage Ddr Sirt1 Trim28 Ubiquitination
DOI10.7150/ijbs.68587
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaBiochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS SubjectBiochemistry & Molecular Biology ; Biology
WOS IDWOS:000782645700001
Scopus ID2-s2.0-85130000307
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Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorShen, Han Ming
Affiliation1.Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
2.State Key Laboratory of Trauma, Burn and Combined Injury, Institute of Burn Research, Southwest Hospital, Army Medical University, Chongqing, China
3.Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
4.Faculty of Health Sciences, University of Macau, Macao
5.Ministry of Education, Frontiers Science Center for Precision Oncology, University of Macau, China
Corresponding Author AffilicationFaculty of Health Sciences;  University of Macau
Recommended Citation
GB/T 7714
Ouyang, Chenxi,Lu, Guang,He, Weifeng,et al. Post-translational Modification in Control of SIRT1 Stability during DNA Damage Response[J]. International Journal of Biological Sciences,2022,18(7):2655-2669.
APA Ouyang, Chenxi,Lu, Guang,He, Weifeng,Bay, Boon Huat,&Shen, Han Ming.(2022).Post-translational Modification in Control of SIRT1 Stability during DNA Damage Response.International Journal of Biological Sciences,18(7),2655-2669.
MLA Ouyang, Chenxi,et al."Post-translational Modification in Control of SIRT1 Stability during DNA Damage Response".International Journal of Biological Sciences 18.7(2022):2655-2669.
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