O-GlcNAcylation of SIRT1 enhances its deacetylase activity and promotes cytoprotection under stress

Han, Cuifang; Gu, Yuchao; Shan, Hui; Mi, Wenyi; Sun, Jiahui; Shi, Minghui; Zhang, Xinling; Lu, Xin; Han, Feng; Gong, Qianhong; Yu, Wengong

doi:10.1038/s41467-017-01654-6

Cited by 94 publications

(78 citation statements)

References 58 publications

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“…However, it is important to note that the decreased glycosylation in SIRT1-mutE2 was not due to reduced interaction with OGT but a resultant of loss of glycosylatable residues T 160 /S 161 within the exon-2 domain ( Figure S2C). Based on our predictions and a concurrent study (Han et al, 2017), we surmise that other sites on SIRT1 could contribute to the residual glycosylation on SIRT1-mutE2.…”

Section: Sirt1 Is Glycosylated Within Its Specificity Domainsupporting

confidence: 53%

Temporal gating of SIRT1 functions by O-GlcNAcylation prevents hyperglycemia and enables physiological transitions in liver

Chattopadhyay

Maniyadath

Bagul

et al. 2019

Preprint

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Inefficient fasted-to-refed transitions are known to cause metabolic diseases. Thus, identifying mechanisms that may constitute molecular switches during such physiological transitions become crucial. Specifically, whether nutrients program a relay of interactions in master regulators, such as SIRT1, and affect their stability is underexplored. Here, we elucidate nutrientdependent O-GlcNAcylation of SIRT1, within its N-terminal domain, as a key determinant of hepatic glucose-and fat-metabolism, and insulin signaling. SIRT1 glycosylation dictates interactions with PPARα/FOXO1/PGC1α/SREBP1, to exert a temporal control over transcription of genes during fasted-to-refed transitions. Interestingly, glycosylation-dependent cytosolic export of SIRT1 promotes a transient interaction with AKT and subsequent proteasomal degradation. Loss of glycosylation discomposes these interactions and enhances stability of SIRT1 even upon refeeding, which causes insulin resistance, hyperglycemia and hepatic-inflammation. Aberrant glycosylation of SIRT1 is associated with aging and/or metabolic diseases. Thus, nutrient-dependent glycosylation constrains spatio-temporal dynamics of SIRT1 and gates its functions to maintain metabolic homeostasis.

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Section: Sirt1 Is Glycosylated Within Its Specificity Domainsupporting

confidence: 53%

Temporal gating of SIRT1 functions by O-GlcNAcylation prevents hyperglycemia and enables physiological transitions in liver

Chattopadhyay

Maniyadath

Bagul

et al. 2019

Preprint

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“…At the molecular level, several key factors, such as GDF9, BMP15, LHR, and Cyp19a, which are essential for ovarian steroidogenesis, follicle development, and oocyte quality, were rescued to levels close to those of the young group. Particularly, in the RTM and MTM groups, the levels of Sirt1, a histone deacetylase whose activity increases during genotoxic, oxidative, or metabolic stress stimuli (Han et al, ), were rescued to levels closest to those in the young group. And moreover, ovary transcriptome study screened more DEGs required for follicle and oocyte quality and these DEGs are involved in multiple KEGG pathways (mTOR, PI3K‐Akt, FoxO, Toll‐like receptor, ErbB, Cytokine–cytokine receptor interaction, oocyte meiosis, apoptosis, etc.)…”

Section: Discussionmentioning

confidence: 99%

Single xenotransplant of rat brown adipose tissue prolonged the ovarian lifespan of aging mice by improving follicle survival

et al. 2019

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Prolonging the ovarian lifespan is attractive and challenging. An optimal clinical strategy must be safe, long‐acting, simple, and economical. Allotransplantation of brown adipose tissue (BAT), which is most abundant and robust in infants, has been utilized to treat various mouse models of human disease. Could we use BAT to prolong the ovarian lifespan of aging mice? Could we try BAT xenotransplantation to alleviate the clinical need for allogeneic BAT due to the lack of voluntary infant donors? In the current study, we found that a single rat‐to‐mouse (RTM) BAT xenotransplantation did not cause systemic immune rejection but did significantly increase the fertility of mice and was effective for more than 5 months (equivalent to 10 years in humans). Next, we did a series of analysis including follicle counting; AMH level; estrous cycle; mTOR activity; GDF9, BMP15, LHR, Sirt1, and Cyp19a level; ROS and annexin V level; IL6 and adiponectin level; biochemical blood indices; body temperature; transcriptome; and DNA methylation studies. From these, we proposed that rat BAT xenotransplantation rescued multiple indices indicative of follicle and oocyte quality; rat BAT also improved the metabolism and general health of the aging mice; and transcriptional and epigenetic (DNA methylation) improvement in F0 mice could benefit F1 mice; and multiple KEGG pathways and GO classified biological processes the differentially expressed genes (DEGs) or differentially methylated regions (DMRs) involved were identical between F0 and F1. This study could be a helpful reference for clinical BAT xenotransplantation from close human relatives to the woman.

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“…RSV is a common activator of SIRT1 (33); both SIRT1 and PARP1 share a common cofactor, NAD + , and several common substrates, including regulators of the DNA damage response (34). As a stress sensor, SIRT1 deacetylase activity is significantly increased during stress (35,36). PCAF is an acetylase and acetylates TyrRS, facilitating its nuclear translocation (13,37).…”

Section: Tyrrs Acetylation Is Regulated By Sirt1mentioning

confidence: 99%

Resveratrol targets TyrRS acetylation to protect against radiation‐induced damage

Gao

et al. 2019

FASEB j.

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Resveratrol (RSV) has broad prospective applications as a radiation protection drug, but its mechanism of action is not yet clear. Here, we found that 5 µM RSV can effectively reduce the cell death caused by irradiation. Irradiation leads to G2/M phase arrest in the cell cycle, whereas RSV treatment increases S‐phase cell cycle arrest, which is associated with sirtuin 1 (SIRT1) regulation. Meanwhile, RSV promotes DNA damage repair, mainly by accelerating the efficiency of homologous recombination repair. Under oxidative stress, tyrosyl‐tRNA synthetase (TyrRS) is transported to the nucleus to protect against DNA damage. RSV can promote TyrRS acetylation, thus promoting TyrRS to enter the nucleus, where it regulates the relevant signaling proteins and reduces apoptosis and DNA damage. SIRT1 is a deacetylase, and SIRT1 knockdown or inhibition can increase TyrRS acetylation levels, further reducing radiation‐induced apoptosis after RSV treatment. Our study revealed a new radiation protection mechanism for RSV, in which the acetylation of TyrRS and its translocation into the nucleus is promoted, and this mechanism may also represent a novel protective target against irradiation.—Gao, P., Li, N., Ji, K., Wang, Y., Xu, C., Liu, Y., Wang, Q., Wang, J., He, N., Sun, Z., Du, L., Liu, Q. Resveratrol targets TyrRS acetylation to protect against radiation‐induced damage. FASEB J. 33, 8083–8093 (2019). http://www.fasebj.org

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O-GlcNAcylation of SIRT1 enhances its deacetylase activity and promotes cytoprotection under stress

Cited by 94 publications

References 58 publications

Temporal gating of SIRT1 functions by O-GlcNAcylation prevents hyperglycemia and enables physiological transitions in liver

Temporal gating of SIRT1 functions by O-GlcNAcylation prevents hyperglycemia and enables physiological transitions in liver

Single xenotransplant of rat brown adipose tissue prolonged the ovarian lifespan of aging mice by improving follicle survival

Resveratrol targets TyrRS acetylation to protect against radiation‐induced damage

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