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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
Published on: March 17, 2016
Regulation of SRC-3 intercompartmental dynamics by estrogen receptor and phosphorylation
Larbi Amazit1, Luigi Pasini, Adam T Szafran
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Molecular and Cellular Biology
|July 25, 2007
Summary
Steroid receptor coactivator 3 (SRC-3) is a nucleocytoplasmic shuttling protein. Its localization and function are regulated by phosphorylation and estrogen receptor alpha (ERalpha) interactions, impacting gene regulation.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Steroid receptor coactivator 3 (SRC-3) is a key p160 family transcription coactivator and oncogene.
- Its precise cellular regulation and functional mechanisms remain incompletely understood.
Purpose of the Study:
- To investigate the dynamic regulation of SRC-3's intracellular mobility, solubility, and localization.
- To elucidate the roles of phosphorylation and estrogen receptor alpha (ERalpha) in controlling SRC-3 function.
Main Methods:
- Utilized live-cell, high-throughput, and fluorescent microscopy.
- Employed chemical inhibition and small interfering RNA (siRNA) to modulate the MEK1/2 pathway.
- Investigated SRC-3 phosphorylation sites and interactions with ERalpha.
Main Results:
- SRC-3 exhibits nucleocytoplasmic shuttling, with localization influenced by MEK1/2 and EGF signaling.
- Phosphorylation at T24, S857, and S860 regulates SRC-3 activity and localization.
- ERalpha presence modulates SRC-3 colocalization, complex formation, and promoter targeting.
Conclusions:
- Phosphorylation is a critical regulator of SRC-3 coactivator function, linking complex formation to cellular compartmentalization.
- These findings provide novel insights into gene regulator mechanisms at the cellular system level.
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