Identification and function of phosphorylation in the glucose-regulated transcription factor ChREBP

The Biochemical Journal
Nikolas G TsatsosHoward C Towle

Abstract

In the liver, induction of genes encoding enzymes involved in de novo lipogenesis occurs in response to increased glucose metabolism. ChREBP (carbohydrate-response-element-binding protein) is a basic helix-loop-helix/leucine zipper transcription factor that regulates expression of these genes. To evaluate the potential role of ChREBP phosphorylation in its regulation, we used MS to identify modified residues. In the present paper, we report the detection of multiple phosphorylation sites of ChREBP expressed in hepatocytes, several of which are only observed under high-glucose conditions. Mutation of each of these serine/threonine residues of ChREBP did not alter its ability to respond to glucose. However, mutation of five N-terminal phosphoacceptor sites resulted in a major decrease in activity under high-glucose conditions. These phosphorylated residues are located within a region of ChREBP (amino acids 1-197) that is critical for glucose regulation. Mutation of Ser(56) within this region to an aspartate residue resulted in increased nuclear accumulation and activity under high-glucose conditions. Together, these data suggest that ChREBP activity is regulated by complex multisite phosphorylation patterns involving its N-termin...Continue Reading

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Citations

Feb 2, 2011·The Journal of Biological Chemistry·Michael BoergesenSusanne Mandrup
Aug 5, 2010·American Journal of Physiology. Endocrinology and Metabolism·Michael N DaviesHoward C Towle
Apr 17, 2012·PloS One·Lisa G McFerrin, William R Atchley
May 8, 2008·Current Opinion in Lipidology·Donald B Jump
Apr 20, 2013·Trends in Endocrinology and Metabolism : TEM·Gaëlle FilhoulaudCatherine Postic
May 13, 2008·Biochemical and Biophysical Research Communications·David T EckertDonald K Scott
Sep 24, 2013·The International Journal of Biochemistry & Cell Biology·Lifang WuXuemei Tong
Apr 2, 2011·Biochimica Et Biophysica Acta·Audrey Poupeau, Catherine Postic
Mar 13, 2012·Seminars in Cell & Developmental Biology·Essi Havula, Ville Hietakangas
May 8, 2008·Current Opinion in Lipidology·Pierre-Damien DenechaudCatherine Postic
Mar 12, 2016·Experimental & Molecular Medicine·Hye-Sook HanSeung-Hoi Koo
Sep 12, 2019·International Journal of Molecular Sciences·Jung-Hwa HanChang-Hoon Woo
Aug 30, 2013·The Journal of Biological Chemistry·Aurélien MichauMaude Le Gall
Oct 19, 2019·International Journal of Molecular Sciences·Ziyi SongFajun Yang
Apr 1, 2008·Molecular and Cellular Biochemistry·Monika Proszkowiec-WeglarzMark P Richards
Apr 5, 2021·The Journal of Biological Chemistry·Liora S KatzMark A Herman
May 8, 2008·Current Opinion in Lipidology

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