A novel role for the cell cycle regulatory complex cyclin D1–CDK4 in gluconeogenesis
نویسندگان
چکیده
Dysregulation of gluconeogenesis is a key pathological feature of type 2 diabetes. However, the molecular mechanisms underlying the regulation of gluconeogenesis remain unclear. Bhalla et al. recently reported that cyclin D1 suppresses hepatic gluconeogenesis through CDK4-dependent phosphorylation of PGC1alpha and consequent inhibition of its activity. The cyclin D1-CDK4 might thus serve as an important link between the cell cycle and control of energy metabolism through modulation of PGC1alpha activity.
منابع مشابه
Cyclin D1 Represses Gluconeogenesis via Inhibition of the Transcriptional Coactivator PGC1α
Hepatic gluconeogenesis is crucial to maintain normal blood glucose during periods of nutrient deprivation. Gluconeogenesis is controlled at multiple levels by a variety of signal transduction and transcriptional pathways. However, dysregulation of these pathways leads to hyperglycemia and type 2 diabetes. While the effects of various signaling pathways on gluconeogenesis are well established, ...
متن کاملCDKs: Much More Than Just the Control of Cell Cycle Progression
Lee and colleagues have shown that CDK4 plays a central role in glucose homeostasis. Insulin activates cyclin D1–CDK4, leading to a decrease in circulating glucose as a consequence of the down-regulation of main genes involved in liver gluconeogenesis.
متن کاملNovel germline CDK4 mutations in patients with head and neck cancer
BACKGROUND Cyclin-dependent kinase 4 (CDK4) together with its regulatory subunit cyclin D1, governs cell cycle progression through G1 phase. Cyclin-dependent kinase inhibitors, including p16INK4A in turn regulate CDK4. In particular, deregulation of the p16/CDK4/cyclin D1 complex has been established in a variety of human tumors including gliomas, sarcomas, melanoma, breast and colorectal cance...
متن کاملAGI December 40/6
Albrecht, Jeffrey H., Brenda M. Rieland, Christopher J. Nelsen, and Cory L. Ahonen. Regulation of G1 cyclindependent kinases in the liver: role of nuclear localization and p27 sequestration. Am. J. Physiol. 277 (Gastrointest. Liver Physiol. 40): G1207–G1216, 1999.—Recent studies suggest that cyclin D1 mediates progression of hepatocytes through G1 phase of the cell cycle. The present study furt...
متن کاملInactivation of the cyclin D-dependent kinase in the rat fibroblast cell line, 3Y1, induced by contact inhibition.
Cyclin-dependent kinase (Cdk) inhibitory proteins are involved in cell cycle arrest induced by antiproliferating factors or chemicals. High cell density also induces cell cycle arrest in which the genomic DNA is unreplicated, even in the presence of a mitotic dose of growth factors; this is termed contact inhibition. Although the cell cycle of the rat fibroblast cell line, 3Y1, was arrested in ...
متن کامل