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Molecular structure and biological function of the cancer-amplified nuclear receptor coactivator SRC-3/AIB1
Lan Liao1, Shao-Qing Kuang, Yuhui Yuan
1Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Abstract:
Nuclear hormone receptors are ligand-dependent transcription factors that require coactivators to regulate target gene expression. The steroid receptor coactivator-3 (SRC-3), also known as p/CIP, RAC3, AIB1, ACTR and TRAM-1, is a cancer-amplified coactivator in the SRC gene family that also contains SRC-1 and TIF2/GRIP1. SRC-3 interacts with nuclear receptors and certain other transcription factors, recruits histone acetyltransferases and methyltransferases for chromatin remodeling and facilitates target gene transcription. Accumulated results from both ex vivo and animal model studies indicate that SRC-3 plays important roles in many biological processes involving cell proliferation, cell migration, cell differentiation, somatic growth, sexual maturation, female reproductive function, vasoprotection and breast cancer. This article summarizes our current knowledge about SRC-3 under the following topics: molecular cloning and characterization; molecular structure and functional mechanisms; SRC-3 as a molecular target of growth factors and cytokines; organization and expression of the SRC-3 gene; generation and characterization of SRC-3 knockout mice; role of SRC-3 in the vasoprotective effects of estrogen; role of SRC-3 in cell migration, proliferation and cancers.
Insights
Steroid receptor coactivator-3 (SRC-3) is a key protein that helps regulate gene expression. This coactivator plays critical roles in cell growth, migration, and various biological processes, including cancer development.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- Nuclear hormone receptors are crucial for regulating gene expression.
- Coactivators, like steroid receptor coactivator-3 (SRC-3), are essential partners for these receptors.
- SRC-3 is amplified in cancer and involved in numerous cellular functions.
Purpose of the Study:
- To summarize the current understanding of SRC-3.
- To explore its molecular mechanisms, gene expression, and biological roles.
- To highlight its involvement in cancer and other physiological processes.
Main Methods:
- Review of ex vivo and animal model studies.
- Analysis of molecular cloning, characterization, and gene organization.
- Investigation of SRC-3 knockout mouse models.
Main Results:
- SRC-3 interacts with transcription factors and recruits chromatin-modifying enzymes.
- It plays significant roles in cell proliferation, migration, differentiation, growth, and reproduction.
- SRC-3 is implicated in the vasoprotective effects of estrogen and breast cancer.
Conclusions:
- SRC-3 is a vital coactivator with diverse biological functions.
- Its dysregulation is linked to cancer progression and other diseases.
- Further research into SRC-3 mechanisms and targets is warranted.