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Cited by 336

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

O-GlcNAc Regulates FoxO Activation in Response to Glucose

Open access
Housley, Michael P., Rodgers, Joseph T., Udeshi, Namrata D., Kelly, Timothy J., Shabanowitz, Jeffrey, Hunt, Donald F., Puigserver, Pere, Hart, Gerald W.·2008·Journal of Biological Chemistry

Abstract

FoxO proteins are key transcriptional regulators of nutrient homeostasis and stress response. The transcription factor FoxO1 activates expression of gluconeogenic, including phosphoenolpyruvate carboxykinase and glucose-6-phosphatase, and also activates the expression of the oxidative stress response enzymes catalase and manganese superoxide dismutase. 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 beta-N-acetylglucosamine (O-GlcNAc) modification. 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. GlcNAcylation of FoxO provides a new mechanism for direct nutrient control of transcription to regulate metabolism and stress response through control of FoxO1 activity.

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Metadata

Authors
Housley, M. P., Rodgers, J. T., Udeshi, N. D., Kelly, T. J., Shabanowitz, J., Hunt, D. F., Puigserver, P., & Hart, G. W.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2008-06
Volume
283
Issue
24
Pages
16283-16292
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2062236151
Cited by
336
References
8
FWCI
8.56
Type
journal article
Language
en
Open access
hybrid

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Housley, M. P., Rodgers, J. T., Udeshi, N. D., Kelly, T. J., Shabanowitz, J., Hunt, D. F., Puigserver, P., & Hart, G. W. (2008). O-GlcNAc Regulates FoxO Activation in Response to Glucose. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m802240200

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