O-GlcNAc regulates FoxO activation in response to glucose.

@article{citeulike:2722983, abstract = {FoxO proteins are key transcriptional regulators of nutrient homeostasis and stress response. The transcription factor FoxO1 activate expression of gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6pc), and also activate the expression of the oxidative stress response enzymes catalase and manganese superoxide dismutase (MnSOD). Hormonal and stress-dependent regulation of FoxO1 via acetylation, ubiquitination, and phosphorylation, are well established, but FoxOs have not been studied in the context of the glucose-derived O-linked ss-Nacetylglucosamine modification (O-GlcNAc). Here we show that O-GlcNAc on hepatic FoxO1 is increased in diabetes. Furthermore, O-GlcNAc regulates FoxO1 activation in response to glucose, resulting in the paradoxically increased expression of gluconeogenic genes while concomitantly inducing expression of genes encoding enzymes that detoxify reactive oxygen species (ROS). GlcNAcylation of FoxO provides a new mechanism for direct nutrient control of transcription to regulate metabolism and stress response through control of FoxO1 activity.}, address = {Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185.}, author = {Housley, Michael P P. and Rodgers, Joseph T T. and Udeshi, Namrata D D. and Kelly, Timothy J J. and Shabanowitz, Jeffrey and Hunt, Donald F F. and Puigserver, Pere and Hart, Gerald W W. }, citeulike-article-id = {2722983}, doi = {http://dx.doi.org/10.1074/jbc.M802240200}, issn = {0021-9258}, journal = {The Journal of biological chemistry}, keywords = {foxo, glcnac, hg}, month = {April}, posted-at = {2008-04-27 04:23:23}, priority = {2}, title = {O-GlcNAc regulates FoxO activation in response to glucose.}, url = {http://dx.doi.org/10.1074/jbc.M802240200}, year = {2008} }

TY - JOUR ID - citeulike:2722983 L3 - citeulike-article-id:2722983 TI - O-GlcNAc regulates FoxO activation in response to glucose. JF - The Journal of biological chemistry AD - Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205-2185. SN - 0021-9258 N2 - FoxO proteins are key transcriptional regulators of nutrient homeostasis and stress response. The transcription factor FoxO1 activate expression of gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (Pepck) and glucose-6-phosphatase (G6pc), and also activate the expression of the oxidative stress response enzymes catalase and manganese superoxide dismutase (MnSOD). Hormonal and stress-dependent regulation of FoxO1 via acetylation, ubiquitination, and phosphorylation, are well established, but FoxOs have not been studied in the context of the glucose-derived O-linked ss-Nacetylglucosamine modification (O-GlcNAc). Here we show that O-GlcNAc on hepatic FoxO1 is increased in diabetes. Furthermore, O-GlcNAc regulates FoxO1 activation in response to glucose, resulting in the paradoxically increased expression of gluconeogenic genes while concomitantly inducing expression of genes encoding enzymes that detoxify reactive oxygen species (ROS). GlcNAcylation of FoxO provides a new mechanism for direct nutrient control of transcription to regulate metabolism and stress response through control of FoxO1 activity. KW - foxo KW - glcnac KW - hg AU - Housley, Michael P AU - Rodgers, Joseph T AU - Udeshi, Namrata D AU - Kelly, Timothy J AU - Shabanowitz, Jeffrey AU - Hunt, Donald F AU - Puigserver, Pere AU - Hart, Gerald W PY - 2008/04/17/ UR - http://dx.doi.org/10.1074/jbc.M802240200 ER -