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p53 represses SV40 transcription by preventing formation of transcription complexes
1Division of Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia.
Abstract:
There is now much evidence to suggest that the p53 tumour suppressor protein functions to monitor the integrity of the genome. When DNA damage is detected, p53 suppresses cell growth to allow repair or directs the cell into apoptosis. The mechanism of action of p53 is as yet unclear but recent evidence has accumulated to suggest that p53 might act by regulating gene expression. Consistent with this model, p53 can both activate and repress a number of viral and cellular promoters. p53 has also been shown to bind to the CCAAT-binding Factor and TATA-binding protein (TBP), and there is direct evidence that p53 represses in vitro transcription by preventing TBP from binding DNA. We now provide evidence that p53 can repress transcription from the SV40 promoter by disrupting DNA/protein complexes involving transcription factor Sp1.
Insights
The p53 tumor suppressor protein monitors genome integrity. New evidence shows p53 represses transcription by disrupting Sp1 DNA binding, impacting gene expression and cell growth regulation.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- The p53 tumor suppressor protein plays a crucial role in maintaining genomic integrity.
- p53 responds to DNA damage by halting cell growth for repair or initiating apoptosis.
- The precise molecular mechanisms by which p53 exerts its functions are still under investigation, with emerging evidence pointing towards gene expression regulation.
Purpose of the Study:
- To investigate the mechanism by which p53 influences gene expression.
- To determine if p53 can repress transcription from specific promoters.
- To elucidate the role of p53 in disrupting DNA-protein complexes involved in transcription.
Main Methods:
- Analysis of p53's interaction with transcription factors.
- In vitro transcription assays.
- Examination of p53's effect on the SV40 promoter.
- Investigation of p53's disruption of DNA/protein complexes involving Sp1.
Main Results:
- p53 demonstrates the ability to both activate and repress viral and cellular promoters.
- p53 interacts with CCAAT-binding Factor and TATA-binding protein (TBP).
- p53 directly represses in vitro transcription by inhibiting TBP binding to DNA.
- p53 represses transcription from the SV40 promoter by disrupting DNA/protein complexes containing transcription factor Sp1.
Conclusions:
- p53 functions as a transcriptional regulator, impacting gene expression.
- p53's repression of transcription, particularly through Sp1 disruption, is a key mechanism in its tumor suppressor activity.
- These findings contribute to understanding how p53 monitors and responds to genomic damage.