Acetylation of glucokinase regulatory protein decreases glucose metabolism by suppressing glucokinase activity

Scientific Reports
Joo-Man ParkYong-Ho Ahn

Abstract

Glucokinase (GK), mainly expressed in the liver and pancreatic β-cells, is critical for maintaining glucose homeostasis. GK expression and kinase activity, respectively, are both modulated at the transcriptional and post-translational levels. Post-translationally, GK is regulated by binding the glucokinase regulatory protein (GKRP), resulting in GK retention in the nucleus and its inability to participate in cytosolic glycolysis. Although hepatic GKRP is known to be regulated by allosteric mechanisms, the precise details of modulation of GKRP activity, by post-translational modification, are not well known. Here, we demonstrate that GKRP is acetylated at Lys5 by the acetyltransferase p300. Acetylated GKRP is resistant to degradation by the ubiquitin-dependent proteasome pathway, suggesting that acetylation increases GKRP stability and binding to GK, further inhibiting GK nuclear export. Deacetylation of GKRP is effected by the NAD(+)-dependent, class III histone deacetylase SIRT2, which is inhibited by nicotinamide. Moreover, the livers of db/db obese, diabetic mice also show elevated GKRP acetylation, suggesting a broader, critical role in regulating blood glucose. Given that acetylated GKRP may affiliate with type-2 diabetes ...Continue Reading

References

Mar 1, 1992·Diabetes Care·A Consoli
Sep 1, 1991·European Journal of Biochemistry·M DetheuxE Van Schaftingen
Apr 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·P B IynedjianA E Renold
Apr 1, 1994·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·E Van SchaftingenM Veiga da Cunha
Oct 28, 1993·Nature·J C ChriviaR H Goodman
Aug 17, 1999·Annual Review of Nutrition·R C NordlieA J Lange
Dec 10, 1999·Proceedings of the National Academy of Sciences of the United States of America·D FarrellyN Hariharan
Nov 8, 2002·The Journal of Biological Chemistry·Muyang LiWei Gu
Nov 29, 2002·The EMBO Journal·Lin-feng ChenWarner C Greene
Dec 31, 2002·JAMA : the Journal of the American Medical Association·Ali H MokdadJames S Marks
May 2, 2003·The Journal of Biological Chemistry·Yan-Hsiung WangSheng-Chung Lee
Nov 18, 2005·Gene·Michele A GlozakEdward Seto
Jun 22, 2006·Proceedings of the National Academy of Sciences of the United States of America·Bjoern SchwerEric Verdin
Oct 19, 2006·Biochemical and Biophysical Research Communications·Ao LiXuebiao Yao
Feb 24, 2007·Endocrinology·Kazuya YoshidaToshihiko Ishida
Jan 18, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Mohammed H MukhtarLoranne Agius
Feb 6, 2008·Cell Metabolism·Bjoern Schwer, Eric Verdin
Sep 17, 2008·Molecular and Cellular Biology·Mukta UllahXiang-Jiao Yang
Apr 18, 2009·Nature Reviews. Drug Discovery·Franz M Matschinsky
Nov 12, 2009·American Journal of Physiology. Endocrinology and Metabolism·Shali ChenSubrata Chakrabarti
Feb 20, 2010·Science·Shimin ZhaoKun-Liang Guan
Oct 12, 2010·Trends in Molecular Medicine·Chao Dai, Wei Gu
Oct 12, 2010·Trends in Biochemical Sciences·Kun-Liang Guan, Yue Xiong
Nov 17, 2010·Biochemical and Biophysical Research Communications·Joo-Man ParkYong-Ho Ahn
Jun 15, 2011·Journal of Molecular Cell Biology·Ying ZhaoWei-Guo Zhu
Jun 19, 2013·Molecular Endocrinology·Ling HeFredric E Wondisford

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Citations

May 27, 2016·Clinical Epigenetics·Vincenzo CarafaLucia Altucci
May 6, 2016·Annual Review of Nutrition·Loranne Agius
Feb 28, 2018·Clinical and Experimental Pharmacology & Physiology·Aneta StachowiczRyszard Korbut
Jul 15, 2017·Antioxidants & Redox Signaling·Mahmoud-Sobhy Elkhwanky, Jukka Hakkola
Jan 4, 2018·Nature Communications·Hitoshi WatanabeHiroshi Inoue
Sep 4, 2016·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marcin BulerJukka Hakkola
Aug 3, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Juan LiFeiruo Huang
Sep 16, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Hana AlkhalidyDongmin Liu
Jan 1, 2021·Bioinformatics·Salvador Casaní-GaldónAna Conesa
May 19, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yue HanShu Chien
Nov 24, 2017·Journal of Proteome Research·Nilmar Silvio MorettiSergio Schenkman

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Methods Mentioned

BETA
ubiquitination
acetylation
co-immunoprecipitation
PCR
transfection
electrophoresis

Software Mentioned

TurboSEQUEST
ZEN
MASCOT
Graphpad Prism

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