Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein
- 6 November 2001
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 98 (24), 13710-13715
- https://doi.org/10.1073/pnas.231370798
Abstract
Recently we purified and identified a previously uncharacterized transcription factor from rat liver binding to the carbohydrate responsive element of the L-type pyruvate kinase (L-PK) gene. This factor was named carbohydrate responsive element binding protein (ChREBP). ChREBP, essential for L-PK gene transcription, is activated by high glucose and inhibited by cAMP. Here, we demonstrated that (i) nuclear localization signal and basic helix-loop-helix/leucine-zipper domains of ChREBP were essential for the transcription, and (ii) these domains were the targets of regulation by cAMP and glucose. Among three cAMP-dependent protein kinase phosphorylation sites, Ser196 and Thr666 were the target sites. Phosphorylation of the former resulted in inactivation of nuclear import, and that of the latter resulted in loss of the DNA-binding activity and L-PK transcription. On the other hand, glucose activated the nuclear import by dephosphorylation of Ser196 in the cytoplasm and also stimulated the DNA-binding activity by dephosphorylation of Thr666 in the nucleus. These results thus reveal mechanisms for regulation of ChREBP and the L-PK transcription by excess carbohydrate and cAMP.Keywords
This publication has 13 references indexed in Scilit:
- A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liverProceedings of the National Academy of Sciences of the United States of America, 2001
- Glucose Regulation of Mouse S14 Gene Expression in HepatocytesPublished by Elsevier BV ,2000
- A Novel Factor Binding to the Glucose Response Elements of Liver Pyruvate Kinase and Fatty Acid Synthase GenesPublished by Elsevier BV ,1999
- Activation of Caspase-1 in the Nucleus Requires Nuclear Translocation of Pro-caspase-1 Mediated by Its ProdomainPublished by Elsevier BV ,1998
- A Novel System to Quantitate Nuclear-Cytoplasmic Fluxin Vivo:Kinetics of Signal-Dependent Nuclear Protein ExportArchives of Biochemistry and Biophysics, 1998
- Transcriptional regulation by glucose in the liverBiochimie, 1997
- Two CACGTG Motifs with Proper Spacing Dictate the Carbohydrate Regulation of Hepatic Gene TranscriptionPublished by Elsevier BV ,1995
- Combinatorial crosstalk of transacting factors binding to the L-type pyruvate kinase promoter elements analysed in vitroBiochemical and Biophysical Research Communications, 1992
- Transcriptional Activities of the Myc and Max Proteins in Mammalian CellsPublished by Springer Science and Business Media LLC ,1992
- Proteins binding to the liver-specific pyruvate kinase gene promoterJournal of Molecular Biology, 1989