Comparative interactomes of <scp>SIRT</scp>6 and <scp>SIRT</scp>7: Implication of functional links to aging

Lee, Namgyu; Kim, Dae-Kyum; Kim, Eung-Sam; Park, Sung Jin; Kwon, Jung‐Hee; Shin, Jihye; Park, Seon‐Min; Moon, Young Ho; Wang, Hee Jung; Gho, Yong Song; Choi, Kwan Yong

doi:10.1002/pmic.201400001

Cited by 78 publications

(92 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The volcano plot presented in Fig. 1B depicts the different Sirt7 interactors including Sirt1, some of which have been described before (16,20,21). A full list of Sirt7 interacting proteins identified in this screen is included in SI Appendix, Dataset S1.…”

Section: Resultsmentioning

confidence: 99%

Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1

Fang

Ianni

Smolka

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Sirtuins (Sirt1-Sirt7) are NAD + -dependent protein deacetylases/ ADP ribosyltransferases, which play decisive roles in chromatin silencing, cell cycle regulation, cellular differentiation, and metabolism. Different sirtuins control similar cellular processes, suggesting a coordinated mode of action but information about potential cross-regulatory interactions within the sirtuin family is still limited. Here, we demonstrate that Sirt1 requires autodeacetylation to efficiently deacetylate targets such as p53, H3K9, and H4K16. Sirt7 restricts Sirt1 activity by preventing Sirt1 autodeacetylation causing enhanced Sirt1 activity in Sirt7 −/− mice. Increased Sirt1 activity in Sirt7 −/− mice blocks PPARγ and adipocyte differentiation, thereby diminishing accumulation of white fat. Thus, reduction of Sirt1 activity restores adipogenesis in Sirt7 −/− adipocytes in vitro and in vivo. We disclosed a principle controlling Sirt1 activity and uncovered an unexpected complexity in the crosstalk between two different sirtuins. We propose that antagonistic interactions between Sirt1 and Sirt7 are pivotal in controlling the signaling network required for maintenance of adipose tissue.sirtuin | acetylation | adipogenesis T he seven sirtuins in mammals (Sirt1-Sirt7) are involved in the regulation of essential cellular processes. Sirtuins rapidly adjust the activity of chromatin, transcription factors, metabolic enzymes, and structural proteins to cellular needs by deacetylating a broad range of targets. The ability to sense metabolic alterations and various stressors enable sirtuins to adapt cellular homeostasis to varying conditions. It seems likely that this feature of sirtuins is crucial to prevent age-dependent pathologies and promote a healthy lifespan (1, 2).Sirt1 is the most widely studied mammalian sirtuin showing the highest homology to the founding member of the sirtuin family, the yeast silence information regulator, Sir2. Sirt1 deacetylates histones H3K9, H3K56, H4K16, and H1K26 as well as many nonhistone targets thereby contributing to the maintenance of metabolic homeostasis and genomic integrity (3, 4). Sirt1 was also identified as a critical component of lifespan extension in response to calorie restriction in several model organisms, although its exact contribution is still under debate (5). The functions of Sirt7 have attracted less attention compared with Sirt1.

show abstract

Section: Resultsmentioning

confidence: 99%

Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1

Fang

Ianni

Smolka

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Similar age-related changes in SIRT7 expression were reported upon cell senescence or aging in other models. Nucleolar SIRT7 protein level decreased in primary human fibroblasts undergoing replicative senescence [19], while the Sirt7 mRNA level decreased in HSCs of old as compared to young mice [7,20]. …”

Section: Discussionmentioning

confidence: 99%

“…Moreover, recent studies suggest that SIRT7 may be involved in the regulation of key metabolic processes [7,8,9,10]. For example, the Sirt7 -/- phenotype was characterized by fatty liver [8,9] which was reverted by liver-specific SIRT7 overexpression, while in normal mice fed high-fat diet overexpression of SIRT7 prevented hepatic steatosis [9].…”

Section: Introductionmentioning

confidence: 99%

Age-Related Changes in Sirtuin 7 Expression in Calorie-Restricted and Refed Rats

et al. 2015

View full text Add to dashboard Cite

Background: Sirtuins (SIRT1-7) have been implicated to mediate the beneficial effects of calorie restriction for healthy aging. While the physiological functions of SIRT7 are still poorly understood, SIRT7 has recently been shown to affect ribosome biogenesis, mitochondrial gene expression, and hepatic lipid metabolism. Objective: To analyze the effects of age and short-term calorie restriction (SCR) and subsequent refeeding on SIRT7 expression in key metabolic tissues. Methods: Four- and 24-month-old male Wistar rats were subjected to 40% SCR for 30 days, followed by ad libitum feeding for 2 or 4 days. Liver, white adipose tissue (WAT), heart and skeletal muscle samples were analyzed by real-time PCR and Western blotting for SIRT7 mRNA and protein expression, respectively. Results: Aging had diverse effects on SIRT7 levels in lipogenic tissues: both the mRNA and protein levels increased in the retroperitoneal depot (rWAT), did not change in the epididymal depot (eWAT), and decreased in the subcutaneous depot (sWAT) and the liver of old as compared to young animals. In the heart, extensor digitorum longus muscle (EDL) and soleus muscle (SOL), Sirt7 gene but not protein expression was lower in old than in young control rats. SCR did not affect SIRT7 expression in WAT and the liver in both age groups. In the heart of young animals, SCR did not affect SIRT7 mRNA or protein level. In EDL, SIRT7 protein but not mRNA levels decreased after SCR and remained reduced upon refeeding. In SOL, both SIRT7 mRNA and protein expression were inhibited by refeeding. In old rats, cardiac Sirt7 expression increased after SCR and refeeding. In old rats' EDL and SOL muscles, SIRT7 protein expression was inhibited by refeeding. Conclusion: Age-related changes of SIRT7 gene expression in key organs of energy homeostasis are tissue dependent.

show abstract

“…The lack of Sirt7 influence on satellite repeats transcription is puzzling in view of the higher Suv39h1 recruitment to the pericentric heterochromatin demonstrated in our paper and requires further investigation. Although there is at present no specific hint that Sirt7 regulates Sirt6 activity directly, both deacetylases share several potential targets implying functional links [29]. Hence, it will be interesting to study the interactive network constituted by Sirt1, Sirt6 and Sirt7, which is based on direct interactions and shared targets, on the structure and compaction of the pericentric heterochromatin.…”

Section: Discussionmentioning

confidence: 99%

Sirt7 inhibits Sirt1-mediated activation of Suv39h1

et al. 2018

View full text Add to dashboard Cite

Sirtuins regulate a variety of cellular processes through protein deacetylation. The best-known member of mammalian sirtuin family, Sirt1, plays important roles in the maintenance of cellular homeostasis by regulating cell metabolism, differentiation and stress responses, among others. Sirt1 activity requires tight regulation to meet specific cellular requirements, which is achieved at different levels and by specific mechanisms. Recently, a regulatory loop between Sirt1 and another sirtuin, Sirt7, was identified. Sirt7 inhibits Sirt1 autodeacetylation at K230 and activation thereby preventing Sirt1-mediated repression of adipocyte differentiation by inhibition of the PPARγ gene. Here, we extend the regulatory complexity of Sirt7-dependent restriction of Sirt1 activity by demonstrating that Sirt7 reduces activation of a previously described prominent Sirt1 target, the histone methyltransferase Suv39h1. We show that removal of the acetyl-group at K230 in Sirt1 due to the absence of Sirt7 leads to hyperactivation of Sirt1 and thereby to constantly increased activity of Suv39h1.

show abstract

Comparative interactomes of SIRT6 and SIRT7: Implication of functional links to aging

Cited by 78 publications

References 61 publications

Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1

Sirt7 promotes adipogenesis in the mouse by inhibiting autocatalytic activation of Sirt1

Age-Related Changes in Sirtuin 7 Expression in Calorie-Restricted and Refed Rats

Sirt7 inhibits Sirt1-mediated activation of Suv39h1

Contact Info

Product

Resources

About