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Published on: September 21, 2011
Steroid receptor coactivator-1 and its family members differentially regulate transactivation by the tumor suppressor
Abstract:
The tumor suppressor protein p53 exerts its cell cycle-regulatory effects through its ability to function as a sequence-specific DNA-binding transcription factor. Herein, we show that p53 physically interacts with specific subregions of steroid receptor coactivator-1 (SRC-1) and its family members, p/CIP (p300/CBP interacting protein), xSRC-3, and AIB1 (amplified in breast cancer), originally isolated as transcription coactivators of nuclear receptors, as demonstrated by the yeast and mammalian two-hybrid tests as well as glutathione S-transferase pull-down assays. Interestingly, cotransfection of HeLa cells with SRC-1- or p/CIP expression vector potentiated the p53-mediated transactivation, whereas AIB1 and xSRC-3 were repressive. All of these SRC-1 members, however, similarly stimulated transactivation mediated by nuclear receptors and AP-1, as previously described. These results suggest that SRC-1 and its family members may differentially modulate the p53 transactivation in vivo.
Insights
The tumor suppressor protein p53 interacts with steroid receptor coactivator-1 (SRC-1) family members. These interactions differentially modulate p53-mediated gene activation, impacting cell cycle regulation.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- The tumor suppressor protein p53 is a transcription factor regulating cell cycle.
- Steroid receptor coactivator-1 (SRC-1) and its family members are coactivators for nuclear receptors.
Purpose of the Study:
- To investigate the interaction between p53 and SRC-1 family members.
- To determine how these interactions affect p53-mediated transactivation.
Main Methods:
- Yeast and mammalian two-hybrid assays.
- Glutathione S-transferase (GST) pull-down assays.
- Cotransfection of HeLa cells with expression vectors.
Main Results:
- p53 physically interacts with SRC-1, p/CIP, xSRC-3, and AIB1.
- SRC-1 and p/CIP potentiated p53-mediated transactivation.
- AIB1 and xSRC-3 repressed p53-mediated transactivation.
- All SRC-1 members stimulated nuclear receptor and AP-1 transactivation.
Conclusions:
- SRC-1 family members differentially modulate p53 transactivation in vivo.
- These findings reveal a novel regulatory mechanism for p53 function.
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