SIRT1 Deacetylates TET2 and Promotes Its Ubiquitination Degradation to Achieve Neuroprotection Against Parkinson's Disease

doi:10.3389/fneur.2021.652882

	SIRT1 Deacetylates TET2 and Promotes Its Ubiquitination Degradation to Achieve Neuroprotection Against Parkinson's Disease
	Li, Xuan 1; Liu, Te 2; Wu, Ting-Ting 1; Feng, Ya 1; Peng, Si-Jia 1; Yin, Huiyong3,4,5 ; Wu, Yun-Cheng 1
	2021-04-15
发表期刊	FRONTIERS IN NEUROLOGY
ISSN	1664-2295
卷号	12
DOI	10.3389/fneur.2021.652882
摘要	The epigenetic modifications, such as DNA methylation and histone acetylation, play a critical role in the pathogenesis of Parkinson's disease (PD). However, the relationship between DNA methylation and histone acetylation in PD is not fully understood. Previous studies have shown that patients with PD exhibit an epigenetic and transcriptional upregulation of Ten-Eleven Translocation 2 (TET2), a member of the DNA hydroxylases family. Silence information regulator 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylase, also plays a critical role in PD development and might be a potential target for PD therapy. Our previous data indicated that demethylation in the Cyclin-dependent kinase inhibitor 2A (CDKN2A) promoter by the TET2 directly activated its expression, then promoted the cell cycle arrest and cell death induced by 1-methyl-4-phenyl-pyridinium ion (MPP+). In this study, we found that the enzyme activity of SIRT1 is negatively correlated with the protein level of TET2. In addition, the deacetylation of TET2 induced by SIRT1 promotes TET2 degradation via the ubiquitin-proteasome pathway. Furthermore, the activation of endogenous SIRT1 by resveratrol (RV) leads to CDKN2A DNA hypermethylation due to the decreased TET2 protein levels, which relieves the inhibitory effect on CDK4 and upregulation of pRb, allowing cell proliferation and growth. Similar effects are observed for the inhibition of endogenous TET2 enzyme activity with TET2 inhibitor. Together, we discover a new mechanism by which the SIRT1-TET2-CDKN2A pathway is involved in the pathogenesis of PD, which may provide a potential target for PD treatment.
关键词	Ten-Eleven Translocation 2 Silence information regulator 1 resveratrol cyclin dependent kinase inhibitor 2A Parkinson&apos s disease
URL	查看原文
收录类别	SCIE
语种	英语
WOS研究方向	Neurosciences & Neurology
WOS类目	Clinical Neurology ; Neurosciences
WOS记录号	WOS:000645118500001
出版者	FRONTIERS MEDIA SA
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/126517
专题	生命科学与技术学院_特聘教授组_尹慧勇组
通讯作者	Yin, Huiyong; Wu, Yun-Cheng
作者单位	1.Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Neurol, Shanghai, Peoples R China; 2.Shanghai Univ Tradit Chinese Med, Shanghai Geriatr Inst Chinese Med, Shanghai, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Nutr Metab & Food Safety, Shanghai, Peoples R China; 4.Minist Hlth, Key Lab Food Safety Risk Assessment, Beijing, Peoples R China; 5.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Li, Xuan,Liu, Te,Wu, Ting-Ting,et al. SIRT1 Deacetylates TET2 and Promotes Its Ubiquitination Degradation to Achieve Neuroprotection Against Parkinson's Disease[J]. FRONTIERS IN NEUROLOGY,2021,12.
APA	Li, Xuan.,Liu, Te.,Wu, Ting-Ting.,Feng, Ya.,Peng, Si-Jia.,...&Wu, Yun-Cheng.(2021).SIRT1 Deacetylates TET2 and Promotes Its Ubiquitination Degradation to Achieve Neuroprotection Against Parkinson's Disease.FRONTIERS IN NEUROLOGY,12.
MLA	Li, Xuan,et al."SIRT1 Deacetylates TET2 and Promotes Its Ubiquitination Degradation to Achieve Neuroprotection Against Parkinson's Disease".FRONTIERS IN NEUROLOGY 12(2021).