Title |
O-GlcNAc Transferase/Host Cell Factor C1 Complex Regulates Gluconeogenesis by Modulating PGC-1α Stability
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Published in |
Cell Metabolism (Science Direct), August 2012
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DOI | 10.1016/j.cmet.2012.07.006 |
Pubmed ID | |
Authors |
Hai-Bin Ruan, Xuemei Han, Min-Dian Li, Jay Prakash Singh, Kevin Qian, Sascha Azarhoush, Lin Zhao, Anton M. Bennett, Varman T. Samuel, Jing Wu, John R. Yates, Xiaoyong Yang |
Abstract |
A major cause of hyperglycemia in diabetic patients is inappropriate hepatic gluconeogenesis. PGC-1α is a master regulator of gluconeogenesis, and its activity is controlled by various posttranslational modifications. A small portion of glucose metabolizes through the hexosamine biosynthetic pathway, which leads to O-linked β-N-acetylglucosamine (O-GlcNAc) modification of cytoplasmic and nuclear proteins. Using a proteomic approach, we identified a broad variety of proteins associated with O-GlcNAc transferase (OGT), among which host cell factor C1 (HCF-1) is highly abundant. HCF-1 recruits OGT to O-GlcNAcylate PGC-1α, and O-GlcNAcylation facilitates the binding of the deubiquitinase BAP1, thus protecting PGC-1α from degradation and promoting gluconeogenesis. Glucose availability modulates gluconeogenesis through the regulation of PGC-1α O-GlcNAcylation and stability by the OGT/HCF-1 complex. Hepatic knockdown of OGT and HCF-1 improves glucose homeostasis in diabetic mice. These findings define the OGT/HCF-1 complex as a glucose sensor and key regulator of gluconeogenesis, shedding light on new strategies for treating diabetes. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 100% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Science communicators (journalists, bloggers, editors) | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
France | 2 | 1% |
Portugal | 1 | <1% |
United Kingdom | 1 | <1% |
Japan | 1 | <1% |
United States | 1 | <1% |
Unknown | 191 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 48 | 24% |
Researcher | 37 | 19% |
Student > Master | 22 | 11% |
Student > Bachelor | 10 | 5% |
Professor > Associate Professor | 9 | 5% |
Other | 29 | 15% |
Unknown | 42 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 57 | 29% |
Biochemistry, Genetics and Molecular Biology | 50 | 25% |
Medicine and Dentistry | 14 | 7% |
Chemistry | 14 | 7% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 2% |
Other | 7 | 4% |
Unknown | 51 | 26% |