Mechanism of BRCA1-mediated inhibition of progesterone receptor transcriptional activity

Related Experiment Video

Updated: Jun 23, 2026

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells
09:24

Silencing of BRCA2 to Identify Novel BRCA2-regulated Biological Functions in Cultured Human Cells

Published on: August 12, 2015

Pragati Katiyar1, Yongxian Ma, Anna Riegel

  • 1Department of Oncology, Lombardi Comprehensive Cancer Center/Georgetown University, Washington, D.C. 20057-1469, USA.

Molecular Endocrinology (Baltimore, Md.)
|April 25, 2009
PubMed

Insights

BRCA1 protein inhibits progesterone receptor (PR) activity by blocking PR binding to DNA and promoting corepressor complex formation, thus reducing gene expression and cell proliferation. This mechanism impacts cancer development.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • BRCA1 protein is known to inhibit progesterone receptor (PR) activity.
  • PR signaling is crucial for progesterone-stimulated gene expression and cell proliferation, often dysregulated in cancers.

Purpose of the Study:

  • To elucidate the mechanism by which BRCA1 inhibits PR activity.
  • To investigate BRCA1's effect on PR binding to progesterone-regulated promoters, specifically c-Myc.

Main Methods:

  • Electrophoretic Mobility Shift Assays (EMSAs) to assess PR-DNA binding.
  • In vitro binding assays with BRCA1 and PR.
  • Chromatin immunoprecipitation assays to analyze coactivator and corepressor recruitment to target gene promoters.

Main Results:

  • BRCA1 does not significantly affect PR ligand-binding affinity.
  • BRCA1 overexpression inhibits PR recruitment to progesterone response elements (PREs) and blocks target gene expression.
  • BRCA1 influences the recruitment of coactivators (AIB1, SRC1) and corepressors (HDAC1) to PREs.

Conclusions:

  • BRCA1 inhibits progestin-stimulated PR activity by impeding PR-DNA binding.
  • BRCA1 promotes the assembly of corepressor complexes over coactivator complexes at target gene promoters.
  • These findings provide mechanistic insights into BRCA1's tumor-suppressive role in hormone-driven cancers.

More Related Videos

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors09:22

Functional Assessment of BRCA1 variants using CRISPR-Mediated Base Editors

Published on: February 28, 2021

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA108:53

Identifying the Effects of BRCA1 Mutations on Homologous Recombination using Cells that Express Endogenous Wild-type BRCA1

Published on: February 17, 2011

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...