Year: 2012
Type: article
Abstract: 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.
Source: Journal of Biological Chemistry
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,430
Funders: Howard Hughes Medical Institute, American Diabetes Association, Ellison Medical Foundation, March of Dimes Foundation, Yale University, Leona M. and Harry B. Helmsley Charitable Trust, China Scholarship Council, National Institutes of Health, National Heart, Lung, and Blood Institute, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G1292148469, G1470717202, O-GlcNAc modification in metabolic homeostasis, G2147928738, G3032035755, G3494256117, G3786517720, Spatial Regulation of Developmental Gene Expression, Glucocorticoid Regulation of NF-kB Function by O-GlcNAc, Nuclear Receptors and Coregulators in Health and Disease, G9000030309, G9000055537, Cancer Center Support Grant (CCSG)
OpenAlex ID: W2068810487