Spatiotemporal gating of SIRT1 functions by O-GlcNAcylation is essential for liver metabolic switching and prevents hyperglycemia.

Proceedings of the National Academy of Sciences of the United States of America
Tandrika ChattopadhyayUllas Kolthur-Seetharam

Abstract

Inefficient physiological transitions are known to cause metabolic disorders. Therefore, investigating mechanisms that constitute molecular switches in a central metabolic organ like the liver becomes crucial. Specifically, upstream mechanisms that control temporal engagement of transcription factors, which are essential to mediate physiological fed-fast-refed transitions are less understood. SIRT1, a NAD+-dependent deacetylase, is pivotal in regulating hepatic gene expression and has emerged as a key therapeutic target. Despite this, if/how nutrient inputs regulate SIRT1 interactions, stability, and therefore downstream functions are still unknown. Here, we establish nutrient-dependent O-GlcNAcylation of SIRT1, within its N-terminal domain, as a crucial determinant of hepatic functions. Our findings demonstrate that during a fasted-to-refed transition, glycosylation of SIRT1 modulates its interactions with various transcription factors and a nodal cytosolic kinase involved in insulin signaling. Moreover, sustained glycosylation in the fed state causes nuclear exclusion and cytosolic ubiquitin-mediated degradation of SIRT1. This mechanism exerts spatiotemporal control over SIRT1 functions by constituting a previously unknown mo...Continue Reading

References

Apr 1, 1992·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·C ChenJ R Turtle
Jan 1, 1997·Annual Review of Biochemistry·G W Hart
May 30, 1998·Proceedings of the National Academy of Sciences of the United States of America·J D HortonH Shimano
Mar 5, 2003·Biochemical and Biophysical Research Communications·Lance WellsGerald W Hart
May 11, 2006·Trends in Endocrinology and Metabolism : TEM·Tianle YangAnthony A Sauve
Jun 20, 2006·Biochimica Et Biophysica Acta·Natasha E Zachara, Gerald W Hart
Jul 29, 2006·Cell·Valter D Longo, Brian K Kennedy
Jan 2, 2007·The Journal of Biological Chemistry·Masaya TannoYoshiyuki Horio
Jul 25, 2007·Proceedings of the National Academy of Sciences of the United States of America·Joseph T Rodgers, Pere Puigserver
Sep 20, 2007·Aging Cell·Laura BordoneLeonard Guarente
Feb 1, 2008·Nature·Ja-Eun KimZhenkun Lou
Jun 4, 2008·The Journal of Biological Chemistry·Stephen A WhelanGerald W Hart
Jun 12, 2008·FEBS Letters·Yariv KanfiHaim Y Cohen
Jul 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Paul T PflugerMatthias H Tschöp
Sep 9, 2008·Biochemical and Biophysical Research Communications·Barbara Zschoernig, Ulrich Mahlknecht
Sep 23, 2008·Trends in Biochemical Sciences·Hye-Sook Kwon, Melanie Ott
Oct 8, 2008·Cell Cycle·Jack FordJo Milner
Oct 9, 2008·Cell Metabolism·Alexander S BanksDomenico Accili
Oct 22, 2008·Trends in Endocrinology and Metabolism : TEM·Tarik Issad, Meishiue Kuo
Dec 25, 2008·PloS One·Tsutomu SasakiHeidi Scrable
May 21, 2009·Nature Reviews. Endocrinology·Fengxia LiangDaisuke Koya
Sep 23, 2009·The Journal of Endocrinology·Mary C SugdenMark J Holness
Oct 13, 2009·Trends in Endocrinology and Metabolism : TEM·Mourad NaïmiEmmanuel Van Obberghen
Dec 23, 2009·PloS One·Nargis NasrinLaura Bordone
Sep 8, 2010·The Journal of Biological Chemistry·Bhaskar PonugotiJongsook Kim Kemper
Nov 26, 2010·Nature Reviews. Cancer·Daniel Herranz, Manuel Serrano
Feb 4, 2011·The FEBS Journal·Deepti RamachandranUllas Kolthur-Seetharam
Feb 25, 2011·Nature Reviews. Molecular Cell Biology·Judith Y Altarejos, Marc Montminy
Oct 4, 2011·Journal of Molecular and Cellular Cardiology·Tsuneaki KawashimaTetsuo Shioi
Oct 12, 2011·The Journal of Clinical Investigation·Simon SchenkJerrold M Olefsky
Oct 19, 2011·The International Journal of Biochemistry & Cell Biology·Sarawut Jitrapakdee
Dec 14, 2011·The Journal of Biological Chemistry·Min PanRonen Marmorstein
Oct 2, 2012·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Chao TongJi Li
Oct 18, 2012·American Journal of Physiology. Endocrinology and Metabolism·Maarten R SoetersJohannes A Romijn
Dec 22, 2012·Acta Biochimica Et Biophysica Sinica·Xiaoling Li
Feb 12, 2013·Trends in Biochemical Sciences·Javier R Revollo, Xiaoling Li
May 7, 2013·Annual Review of Nutrition·Michelle R Bond, John A Hanover

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Citations

Apr 3, 2020·Journal of Clinical Medicine·Sarthak SahooMohit Kumar Jolly
Feb 13, 2021·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Laetitia KoppeDenis Fouque
Mar 17, 2021·Cell Death Discovery·Zhipeng TaoZhiyong Cheng
Mar 21, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Xiaozhen ZhangShemin Lu
Apr 24, 2021·Genes & Development·Lara BideyanPeter Tontonoz
Oct 8, 2021·Proceedings of the National Academy of Sciences of the United States of America·Namrata ShuklaUllas Kolthur-Seetharam

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