Advances in Cellular Characterization of the Sirtuin Isoform, SIRT7

Wu, Di; Li, Yinglu; Zhu, Kathy S.; Wang, Haiying; Zhu, Weiguo

doi:10.3389/fendo.2018.00652

Cited by 70 publications

(48 citation statements)

References 90 publications

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“…Sirtuin 7 (SIRT7) is a nicotinamide adenine dinucleotide (NAD + )-dependent histone deacetylase that predominantly localizes to the nucleus. It has been implicated in diverse cellular processes, including aging, DNA repair, tumorigenesis, and metabolism [1][2][3][4]. SIRT7 is activated by an elevated NAD + /NADH ratio [5], thus SIRT7 has emerged as an important energy sensor in mammals [6,7].…”

Section: Introductionmentioning

confidence: 99%

SIRT7 activates p53 by enhancing PCAF-mediated MDM2 degradation to arrest the cell cycle

et al. 2020

Oncogene

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Sirtuin 7 (SIRT7), an NAD +-dependent deacetylase, plays vital roles in energy sensing, but the underlying mechanisms of action remain less clear. Here, we report that SIRT7 is required for p53-dependent cell-cycle arrest during glucose deprivation. We show that SIRT7 directly interacts with p300/CBP-associated factor (PCAF) and the affinity for this interaction increases during glucose deprivation. Upon binding, SIRT7 deacetylates PCAF at lysine 720 (K720), which augments PCAF binding to murine double minute (MDM2), the p53 E3 ubiquitin ligase, leading to accelerated MDM2 degradation. This effect results in upregulated expression of the cell-cycle inhibitor, p21 Waf1/Cip1 , which further leads to cellcycle arrest and decreased cell viability. These data highlight the importance of the SIRT7-PCAF interaction in regulating p53 activity and cell-cycle progression during conditions of glucose deprivation. This axis may represent a new avenue to design effective therapeutics based on tumor starvation.

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Section: Introductionmentioning

confidence: 99%

SIRT7 activates p53 by enhancing PCAF-mediated MDM2 degradation to arrest the cell cycle

et al. 2020

Oncogene

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“…When we reinforced Sirt7 in old mice by overexpression, we observed a significant improvement in agingassociated hair dysfunction. Sirt1 and Sirt6 possess stronger deacetylase activity than Sirt7 (Wu et al, 2018): This finding elicits the interesting question of whether Sirt1, Sirt6, and Sirt7 have redundant roles in HFSCs. Unlike Sirt7, we did not observe any obvious or strong interaction between Sirt1, Sirt2, Sirt6, and Nfatc1 (Appendix Fig S4F), suggesting that these sirtuin family members are unlikely to act as Nfatc1 deacetylases in this context.…”

Section: Discussionmentioning

confidence: 82%

“…The sirtuin protein family is involved in regulating longevity (Wu et al, 2018). Data from phenotypic analyses of knockout mice suggest that Sirt1, Sirt6, and Sirt7 are potential longevity-associated genes (Vakhrusheva et al, 2008;Kawahara et al, 2009;Kanfi et al, 2012;Satoh et al, 2013;Vazquez et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Data from phenotypic analyses of knockout mice suggest that Sirt1, Sirt6, and Sirt7 are potential longevity-associated genes (Vakhrusheva et al, 2008;Kawahara et al, 2009;Kanfi et al, 2012;Satoh et al, 2013;Vazquez et al, 2016). Sirt7 is an NAD +dependent deacylase and its expression declines in senescent cells (Blank & Grummt, 2017;Wu et al, 2018). Many studies have uncovered links between Sirt7 and aging: Sirt7 À/À mice have a shortened lifespan by up to 50% and exhibit multiple aging phenotypes, including hepatic steatosis, gonadal fat pad content depletion, cardiac hypertrophy, and hematopoietic stem cell reduction (Shin et al, 2013;Ryu et al, 2014;Yoshizawa et al, 2014;Araki et al, 2015;Mohrin et al, 2015;Tang, 2015;Vazquez et al, 2016;Tang et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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SIRT 7 activates quiescent hair follicle stem cells to ensure hair growth in mice

Tang

Zhang

et al. 2020

The EMBO Journal

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Hair follicle stem cells (HFSCs) are maintained in a quiescent state until activated to grow, but the mechanisms that reactivate the quiescent HFSC reservoir are unclear. Here, we find that loss of Sirt7 in mice impedes hair follicle life‐cycle transition from telogen to anagen phase, resulting in delay of hair growth. Conversely, Sirt7 overexpression during telogen phase facilitated HSFC anagen entry and accelerated hair growth. Mechanistically, Sirt7 is upregulated in HFSCs during the telogen‐to‐anagen transition, and HFSC‐specific Sirt7 knockout mice (Sirt7f/f;K15‐Cre) exhibit a similar hair growth delay. At the molecular level, Sirt7 interacts with and deacetylates the transcriptional regulator Nfatc1 at K612, causing PA28γ‐dependent proteasomal degradation to terminate Nfatc1‐mediated telogen quiescence and boost anagen entry. Cyclosporin A, a potent calcineurin inhibitor, suppresses nuclear retention of Nfatc1, abrogates hair follicle cycle delay, and promotes hair growth in Sirt7−/− mice. Furthermore, Sirt7 is downregulated in aged HFSCs, and exogenous Sirt7 overexpression promotes hair growth in aged animals. These data reveal that Sirt7 activates HFSCs by destabilizing Nfatc1 to ensure hair follicle cycle initiation.

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“…Motif analysis of hyper-methylated DMRs uncovered the disproportionate methylation of promoter targets for ETS domain-containing transcription factor ELK4. As a regulator of numerous proto-oncogenes, ELK4 is believed to regulate malignant transformation in the context of multiple cancer types (Wu et al, 2018). Specifically, ELK4 has been shown to recruit and stabilize epigenetic regulator SIRT7 to promote tumor growth and maintain rapid cellular proliferation (Makkonen et al, 2008;Day et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Differential DNA Methylation Encodes Proliferation and Senescence Programs in Human Adipose-Derived Mesenchymal Stem Cells

et al. 2020

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Adult adipose tissue-derived mesenchymal stem cells (ASCs) constitute a vital population of multipotent cells capable of differentiating into numerous end-organ phenotypes. However, scientific and translational endeavors to harness the regenerative potential of ASCs are currently limited by an incomplete understanding of the mechanisms that determine cell-lineage commitment and stemness. In the current study, we used reduced representation bisulfite sequencing (RRBS) analysis to identify epigenetic gene targets and cellular processes that are responsive to 5-azacitidine (5-AZA). We describe specific changes to DNA methylation of ASCs, uncovering pathways likely associated with the enhancement of their proliferative capacity. We identified 4,797 differentially methylated regions (FDR < 0.05) associated with 3,625 genes, of which 1,584 DMRs annotated to the promoter region. Gene set enrichment of differentially methylated promoters identified "phagocytosis," "type 2 diabetes," and "metabolic pathways" as disproportionately hypomethylated, whereas "adipocyte differentiation" was the most-enriched pathway among hyper-methylated gene promoters. Weighted coexpression network analysis of DMRs identified clusters associated with cellular proliferation and other developmental programs. Furthermore, the ELK4 binding site was disproportionately hyper-methylated within the promoters of genes associated with AKT signaling. Overall, this study offers numerous preliminary insights into the epigenetic landscape that influences the regenerative capacity of human ASCs.

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Advances in Cellular Characterization of the Sirtuin Isoform, SIRT7

Cited by 70 publications

References 90 publications

SIRT7 activates p53 by enhancing PCAF-mediated MDM2 degradation to arrest the cell cycle

SIRT7 activates p53 by enhancing PCAF-mediated MDM2 degradation to arrest the cell cycle

SIRT 7 activates quiescent hair follicle stem cells to ensure hair growth in mice

Differential DNA Methylation Encodes Proliferation and Senescence Programs in Human Adipose-Derived Mesenchymal Stem Cells

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