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CREB-regulated transcription coactivator 2 (CRTC2) is a coregulator of the progesterone and glucocorticoid receptor

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • MJ Hill
  • JH Segars
  • T Kino


Objective:. We hypothesized that CRTC2 might influence the transcriptional activity of progesterone receptor (PR) and glucocorticoid receptor (GR), mediating nutritional signals to the action of these receptors. Methods: Transient transfection-based reporter assays tested the effect of CRTC2 over-expression on the transcriptional activity of PR and GR. HeLa and T47D cells were treated with progesterone- and glucocorticoid-responsive MMTV luciferase gene, CRTC2-expressing plasmids, and ligand. Knockdown experiments using CRTC2 siRNA in T47D examined mRNA expression of the endogenous PR and GR-responsive genes with rtPCR. GST pulldown assays and mammalian two-hybrid assays examined protein interactions. Results: CRTC2 overexpression enhanced the transcriptional activity of GR and decreased the PR activity. CRCT2 overexpression shifted dexamethasone and progesterone titration reporter assay curve activity up- and down-ward, respectively. CRTC2 knockdown with its siRNA decreased GR responsive GILZ mRNA expression but increased PR responsive KLF5 mRNA expression. Overexpression of AMPK decreased PR activity whether CRTC2 was overexpressed or knocked down. CRTC2 overexpression of activating mutations at phosphorylation sites 275 and 307 increased GR activity as compared to wild type CRTC2. CRTC2 N-terminal bound most strongly to both receptors LBDs. Conclusions: Our results suggest that CRTC2 acts as a coregulator for some steroid hormone receptors.

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