O-GlcNAc transferase is involved in glucocorticoid receptor-mediated transrepression.

Authors:
Dr. Min-Dian Li, PhD
Dr. Min-Dian Li, PhD
Harvard TH Chan School of Public Health
Postdoctoral Fellow
Cellular and Molecular Physiology
Boston, MA | United States
Hai-Bin Ruan
Hai-Bin Ruan
United States
Jay P Singh
Jay P Singh
University of Oxford
United Kingdom
Lin Zhao
Lin Zhao
College of Automation
China
Tingting Zhao
Tingting Zhao
Institute of Immunology
New Delhi | India
Sascha Azarhoush
Sascha Azarhoush
United States
Jing Wu
Jing Wu
Jiangnan University
China
Ronald M Evans
Ronald M Evans
Gene Expression Laboratory
San Diego | United States

J Biol Chem 2012 Apr 27;287(16):12904-12. Epub 2012 Feb 27.

Department of Cellular and Molecular Physiology, Section of Comparative Medicine and Program in Integrative Cell Signaling and Neurobiology of Metabolism, Yale University School of Medicine, New Haven, Connecticut 06520, USA.

Recruitment of O-GlcNAc transferase (OGT) to promoters plays an important role in gene repression. Glucocorticoid signaling represses the transcriptional activities of NF-κB and AP-1 through direct binding, yet the molecular mechanisms remain to be elucidated. Here we report that OGT is an important component of GR-mediated transrepression. OGT associates with ligand-bound GR in a multi-protein repression complex. Overexpression of OGT potentiates the GR transrepression pathway, whereas depletion of endogenous OGT by RNA interference abolishes the repression. The recruitment of OGT by GR leads to increased O-GlcNAcylation and decreased phosphorylation of RNA polymerase II on target genes. Functionally, overexpression of OGT enhances glucocorticoid-induced apoptosis in resistant cell lines while knockdown of OGT prevents sensitive cell lines from apoptosis. These studies identify a molecular mechanism of GR transrepression, and highlight the function of O-GlcNAc in hormone signaling.

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Source
http://dx.doi.org/10.1074/jbc.M111.303792DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3339970PMC

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April 2012
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