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Ubiquitin-specific peptidase 7 (USP7)-mediated deubiquitination of the histone deacetylase SIRT7 regulates gluconeogenesis
| Content Provider | Scilit |
|---|---|
| Author | Jiang, Lu Xiong, Jiannan Zhan, Junsi Yuan, Fengjie Tang, Ming Zhang, Chaohua Cao, Ziyang Chen, Yongcan Lu, Xiaopeng Li, Yinglu Wang, Hui Wang, Lina Wang, Jiadong Zhu, Wei-Guo Wang, Haiying |
| Copyright Year | 2017 |
| Description | Journal: Journal of Biological Chemistry Sirtuin 7 (SIRT7), a member of the $NAD^{+}$-dependent class III histone deacetylases, is involved in the regulation of various cellular processes and in resisting various stresses, such as hypoxia, low glucose levels, and DNA damage. Interestingly, SIRT7 is linked to the control of glycolysis, suggesting a role in glucose metabolism. Given the important roles of SIRT7, it is critical to clarify how SIRT7 activity is potentially regulated. It has been reported that some transcriptional and post-transcriptional regulatory mechanisms are involved. However, little is known how SIRT7 is regulated by the post-translational modifications. Here, we identified ubiquitin-specific peptidase 7 (USP7), a deubiquitinase, as a negative regulator of SIRT7. We showed that USP7 interacts with SIRT7 both in vitro and in vivo, and we further demonstrated that SIRT7 undergoes endogenous Lys-63-linked polyubiquitination, which is removed by USP7. Although the USP7-mediated deubiquitination of SIRT7 had no effect on its stability, the deubiquitination repressed its enzymatic activity. We also showed that USP7 coordinates with SIRT7 to regulate the expression of glucose-6-phosphatase catalytic subunit (G6PC), a gluconeogenic gene. USP7 depletion by RNA interference increased both G6PC expression and SIRT7 enzymatic activity. Moreover, SIRT7 targeted the G6PC promoter through the transcription factor ELK4 but not through forkhead box O1 (FoxO1). In summary, SIRT7 is a USP7 substrate and has a novel role as a regulator of gluconeogenesis. Our study may provide the basis for new clinical approaches to treat metabolic disorders related to glucose metabolism. |
| Related Links | http://www.jbc.org/content/292/32/13296.full.pdf https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555190/pdf http://www.jbc.org/article/S0021925820385562/pdf |
| Ending Page | 13311 |
| Page Count | 16 |
| Starting Page | 13296 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.m117.780130 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 32 |
| Volume Number | 292 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2017-08-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Deubiquitylation (deubiquitination) Post-translational Modification |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
