Related Experiment Video

Updated: Jun 16, 2026

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation
09:07

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation

Published on: June 21, 2016

Identification of SRC3/AIB1 as a preferred coactivator for hormone-activated androgen receptor

X Edward Zhou1, Kelly M Suino-Powell, Jun Li

  • 1Laboratory of Structural Sciences, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA.

The Journal of Biological Chemistry
|January 21, 2010
PubMed

Insights

Androgen receptor (AR) and steroid receptor coactivator-3 (SRC3) interaction is crucial for prostate cancer progression. This study reveals SRC3 is a preferred coactivator for hormone-activated AR, linking their relationship to cancer development.

Area of Science:

  • Molecular Biology
  • Oncology
  • Structural Biology

Background:

  • Androgen receptor (AR) activation is essential for prostate cancer initiation and progression.
  • AR's interaction with coactivators is critical but not fully understood.
  • AR uniquely utilizes its N-terminal FXXLF motif over canonical coactivator LXXLL motifs.

Purpose of the Study:

  • To elucidate the molecular mechanism of hormone-activated AR's interaction with coactivators.
  • To investigate the role of steroid receptor coactivator-3 (SRC3) in AR-mediated transcription.
  • To determine the significance of the AR-SRC3 interaction in prostate cancer.

Main Methods:

  • Biochemical assays to study protein-protein interactions.
  • Crystallographic studies to determine the structural basis of AR-SRC3 binding.
  • Mutagenesis and functional studies to validate the role of SRC3.
  • Analysis of AR mutations in prostate cancer patients.

Main Results:

  • Steroid receptor coactivator-3 (SRC3) binds strongly to hormone-activated AR via its first and third LXXLL motifs.
  • SRC3 is identified as a preferred coactivator for hormone-activated AR.
  • AR mutations found in prostate cancer patients show altered binding affinity to SRC3.
  • SRC3's role as a prostate cancer oncogene is supported.

Conclusions:

  • A molecular mechanism for selective SRC3 utilization by hormone-activated AR is provided.
  • The functional relationship between AR and SRC3 is directly linked to prostate cancer development and growth.
  • SRC3 represents a potential therapeutic target in prostate cancer.

More Related Videos

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay09:07

Detecting the Ligand-binding Domain Dimerization Activity of Estrogen Receptor Alpha Using the Mammalian Two-Hybrid Assay

Published on: December 19, 2018

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists10:51

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists

Published on: November 15, 2013

Related Concept Videos

Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Co-activators and Co-repressors02:04

Co-activators and Co-repressors

Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
Internal Receptors01:31

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.
Secondary Messengers in Hormone Action01:26

Secondary Messengers in Hormone Action

Water-soluble hormones cannot cross the plasma membrane, so they rely on protein receptors that span the membrane to trigger intracellular signaling pathways. These pathways then activate second messengers inside the cell, including cAMP or calcium ions.
Many hormones bind to transmembrane G protein-coupled receptors that connect to regulatory G proteins. These G proteins can then activate enzymes such as adenylyl cyclase or phospholipase C. Adenylyl cyclase converts ATP to cAMP, activating...
Intracellular Hormone Receptors01:08

Intracellular Hormone Receptors

Lipid-soluble hormones diffuse across the plasma and nuclear membrane of target cells to bind to their specific intracellular receptors. These receptors act as transcription factors that regulate gene expression and protein synthesis in the target cell
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes: