Related Experiment Video

Updated: Apr 12, 2026

Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
10:51

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

Published on: November 15, 2013

13.2K

The pERK of being a target: Kinase regulation of the orphan nuclear receptor ERRγ

Rebecca B Riggins1

  • 1Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057 USA.

Receptors & Clinical Investigation
|May 26, 2015
PubMed

Insights

Estrogen-related receptor gamma (ERRγ) is regulated by extracellular signal-regulated kinase (ERK). This interaction impacts ERRγ function in estrogen receptor-positive breast cancer models, offering new molecular and clinical insights.

Area of Science:

  • Molecular endocrinology
  • Cancer biology
  • Nuclear receptor signaling

Background:

  • Estrogen-related receptors (ERRs) are orphan nuclear receptors regulating mitochondrial metabolism and implicated in cancer.
  • ERRs lack endogenous ligands, relying on alternative regulatory mechanisms like post-translational modification.
  • The clinical significance of ERR post-translational modification remains largely undefined.

Purpose of the Study:

  • To investigate the regulatory role of extracellular signal-regulated kinase (ERK) on estrogen-related receptor gamma (ERRγ).
  • To determine the functional consequences of ERK-mediated regulation of ERRγ in breast cancer.
  • To explore the molecular and clinical implications of ERRγ regulation by ERK.

Main Methods:

  • Utilized cellular models of estrogen receptor-positive (ER+) breast cancer.
  • Investigated protein-protein interactions between ERK and ERRγ.
  • Assessed the functional impact of ERRγ regulation by ERK on cellular processes.

Main Results:

  • Established estrogen-related receptor gamma (ERRγ) as a direct target of extracellular signal-regulated kinase (ERK).
  • Demonstrated that ERK regulation of ERRγ significantly affects its function in ER+ breast cancer cells.
  • Identified specific consequences for ERRγ activity mediated by ERK.

Conclusions:

  • ERK-mediated regulation of ERRγ is a key mechanism influencing its role in breast cancer.
  • These findings provide a molecular basis for understanding ERRγ function in cancer.
  • The study highlights potential therapeutic avenues targeting the ERRγ-ERK axis in breast cancer treatment.
Keywords:
ERK/MAPKERRgammaESRRGorphan nuclear receptortamoxifentranscription

More Related Videos

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation09:07

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

Published on: June 21, 2016

8.8K
Spatial and Temporal Analysis of Active ERK in the C. elegans Germline08:40

Spatial and Temporal Analysis of Active ERK in the C. elegans Germline

Published on: November 29, 2016

10.9K

Related Concept Videos

The Unfolded Protein Response01:37

The Unfolded Protein Response

The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
7.1K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.2K
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:
6.2K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
3.5K
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...
9.0K
Directing Proteins to the Rough Endoplasmic Reticulum01:34

Directing Proteins to the Rough Endoplasmic Reticulum

The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
18.4K