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Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
Published on: October 4, 2024
Role of the steroid receptor coactivator SRC-3 in cell growth
Ge Zhou1, Yoshihiro Hashimoto, Inseok Kwak
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Abstract:
Steroid receptor coactivator 3 (SRC-3/p/CIP/AIB1/ACTR/RAC3/TRAM-1) is a member of the p160 family of nuclear receptor coactivators, which includes SRC-1 (NCoA-1) and SRC-2 (TIF2/GRIP1/NCoA2). Previous studies indicate that SRC-3 is required for normal animal growth and is often amplified or overexpressed in many cancers, including breast and prostate cancers. However, the mechanisms of SRC-3-mediated growth regulation remain unclear. In this study, we show that overexpression of SRC-3 stimulates cell growth to increase cell size in prostate cancer cell lines. Furthermore, our results indicate that overexpression of SRC-3 can modulate the AKT signaling pathway in a steroid-independent manner, which results in the activation of AKT/mTOR signaling concomitant with an increase in cell size. In contrast, down-regulation of SRC-3 expression in cells by small interfering RNA decreases cell growth, leading to a smaller cell size. Similarly, in SRC-3 null mutant mice, AKT signaling is down-regulated in normally SRC-3-expressing tissues. Taken together, these results suggest that SRC-3 is an important modulator for mammalian cell growth.
Insights
Steroid receptor coactivator 3 (SRC-3) promotes mammalian cell growth by activating AKT/mTOR signaling. Reducing SRC-3 levels decreases cell size, highlighting its role in growth regulation.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Steroid receptor coactivator 3 (SRC-3) is a p160 family member implicated in normal animal growth.
- SRC-3 is frequently amplified or overexpressed in various cancers, including breast and prostate cancers.
- The precise mechanisms underlying SRC-3's role in growth regulation are not fully understood.
Purpose of the Study:
- To investigate the role of SRC-3 in regulating cell growth and size.
- To elucidate the signaling pathways modulated by SRC-3 during cell growth.
- To determine the impact of SRC-3 modulation on AKT signaling.
Main Methods:
- Overexpression of SRC-3 in prostate cancer cell lines.
- Down-regulation of SRC-3 using small interfering RNA (siRNA).
- Analysis of AKT signaling pathway activation.
- Examination of SRC-3 null mutant mice.
Main Results:
- SRC-3 overexpression significantly increased cell size in prostate cancer cells.
- SRC-3 modulated the AKT signaling pathway independently of steroids, activating AKT/mTOR signaling.
- SRC-3 down-regulation led to decreased cell growth and smaller cell size.
- AKT signaling was reduced in SRC-3 null mutant mice tissues.
Conclusions:
- SRC-3 is a critical regulator of mammalian cell growth.
- SRC-3 influences cell size through modulation of the AKT/mTOR signaling pathway.
- These findings provide insights into SRC-3's function in both normal growth and cancer development.
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