Sirtuin 7 Plays a Role in Ribosome Biogenesis and Protein Synthesis

Tsai, Yuan Chin; Greco, Todd M.; Cristea, Ileana M.

doi:10.1074/mcp.m113.031377

Cited by 105 publications

(102 citation statements)

References 38 publications

(72 reference statements)

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“…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.

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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.

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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.

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“…Sirt7 is known to inhibit autophagy through its interaction with mammalian target of rapamycin. 24 Therefore, it is reasonable to hypothesize that Sirt7-dependent TβRI regulation is mediated by autophagy. In this regard, we found that Sirt7 mediates some of its effects by interaction with PICK1.…”

Section: Discussionmentioning

confidence: 99%

“…24 Loss of Sirt7 accelerated TβRI breakdown in rat cardiac fibroblasts and mouse dermal fibroblasts after starvation ( Figure 5A and Figure VIIA in the online-only Data Supplement). Accordingly, we investigated in the next series of experiments whether Sirt7 regulates TβRI protein by modulating the autophagy pathway.…”

Section: Sirt7 Maintains Tβri Protein By Interacting With Protein Intmentioning

confidence: 99%

Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway

et al. 2015

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Background— Sirt7, 1 of the 7 members of the mammalian sirtuin family, promotes oncogenic transformation. Tumor growth and metastasis require fibrotic and angiogenic responses. Here, we investigated the role of Sirt7 in cardiovascular tissue repair process. Methods and Results— In wild-type mice, Sirt7 expression increased in response to acute cardiovascular injury, including myocardial infarction and hind-limb ischemia, particularly at the active wound healing site. Compared with wild-type mice, homozygous Sirt7-deficient (Sirt7 −/− ) mice showed susceptibility to cardiac rupture after myocardial infarction, delayed blood flow recovery after hind-limb ischemia, and impaired wound healing after skin injury. Histological analysis showed reduced fibrosis, fibroblast differentiation, and inflammatory cell infiltration in the border zone of infarction in Sirt7 −/− mice. In vitro, Sirt7 −/− mouse–derived or Sirt7 siRNA–treated cardiac fibroblasts showed reduced transforming growth factor-β signal activation and low expression levels of fibrosis-related genes compared with wild-type mice–derived or control siRNA–treated cells. These changes were accompanied by reduction in transforming growth factor receptor I protein. Loss of Sirt7 activated autophagy in cardiac fibroblasts. Transforming growth factor-β receptor I downregulation induced by loss of Sirt7 was blocked by autophagy inhibitor, and interaction of Sirt7 with protein interacting with protein kinase-Cα was involved in this process. Conclusion— Sirt7 maintains transforming growth factor receptor I by modulating autophagy and is involved in the tissue repair process.

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“…Levels of newly synthesized protein were estimated using a nonisotopic labeling method as described previously (19), with a Click-it HPG Alexa Fluor 488 protein synthesis assay kit (Life Technologies). Briefly, primary bone marrow-derived macrophages were grown for 30 min in RPMI 1640 medium without methionine (Life Technologies) and supplemented with 50 M L-homopropargylglycine (HPG).…”

Section: Methodsmentioning

confidence: 99%

Involvement of RNA Polymerase III in Immune Responses

Graczyk

White

Ryan

2015

Molecular and Cellular Biology

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bInflammation in the tumor microenvironment has many tumor-promoting effects. In particular, tumor-associated macrophages (TAMs) produce many cytokines which can support tumor growth by promoting survival of malignant cells, angiogenesis, and metastasis. Enhanced cytokine production by TAMs is tightly coupled with protein synthesis. In turn, translation of proteins depends on tRNAs, short abundant transcripts that are made by RNA polymerase III (Pol III). Here, we connect these facts by showing that stimulation of mouse macrophages with lipopolysaccharides (LPS) from the bacterial cell wall causes transcriptional upregulation of tRNA genes. The transcription factor NF-B is a key transcription factor mediating inflammatory signals, and we report that LPS treatment causes an increased association of the NF-B subunit p65 with tRNA genes. In addition, we show that p65 can directly associate with the Pol III transcription factor TFIIIB and that overexpression of p65 induces Pol IIIdependent transcription. As a consequence of these effects, we show that inhibition of Pol III activity in macrophages restrains cytokine secretion and suppresses phagocytosis, two key functional characteristics of these cells. These findings therefore identify a radical new function for Pol III in the regulation of macrophage function which may be important for the immune responses associated with both normal and malignant cells.

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Sirtuin 7 Plays a Role in Ribosome Biogenesis and Protein Synthesis

Cited by 105 publications

References 38 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

Sirt7 Contributes to Myocardial Tissue Repair by Maintaining Transforming Growth Factor-β Signaling Pathway

Involvement of RNA Polymerase III in Immune Responses

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