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Transcriptional antagonism between p53 and sv40 T-antigen
Abstract:
In this communication we show that overexpression of the human TATA-binding protein (TBP) activates a synthetic promoter with p53-binding sites in the presence of wild-type p53. No activation is observed in the absence of wild-type p53 in Saos-2 cells. Perhaps, TBP is limiting in these cells for the p53-mediated activation, and p53 activates promoters with p53-binding sites via its interaction with TBP. Using in vivo transient transfection-transcription assays, we also show that wild-type human p53 inhibits simian virus 40 (SV40) late promoter transactivation by SV40 T antigen, but excess T antigen partially releases this inhibition. Recently both T antigen and p53 have been shown to interact with TBP. The inhibition of T antigen-mediated SV40 late promoter activation by p53 or the inhibition of p53-mediated activation of a promoter with p53-binding sites by T antigen is not released by an overexpression of TBP. Thus, the transcriptional antagonism between p53 and T antigen are not at the level of competition for TBP. Possibly, the two proteins poison each other so that they cannot interact with the transcription machinery.
Insights
Overexpression of human TATA-binding protein (TBP) activates p53-mediated transcription. However, TBP does not resolve the transcriptional antagonism between p53 and SV40 T antigen, suggesting a different inhibitory mechanism.
Area of Science:
- Molecular Biology
- Transcriptional Regulation
- Oncogenes
Background:
- The TATA-binding protein (TBP) is a crucial transcription factor.
- Wild-type p53 is a tumor suppressor protein involved in transcriptional regulation.
- Simian virus 40 (SV40) T antigen is a viral oncoprotein that can alter cellular transcription.
Purpose of the Study:
- To investigate the role of TBP in p53-mediated transcriptional activation.
- To explore the interaction between p53, SV40 T antigen, and TBP in regulating transcription.
Main Methods:
- In vivo transient transfection-transcription assays were employed.
- Overexpression of human TBP was utilized.
- Saos-2 cells were used to assess p53-dependent activation.
Main Results:
- Overexpression of TBP activated a synthetic promoter with p53-binding sites in the presence of wild-type p53, but not in its absence.
- Wild-type p53 inhibited SV40 late promoter transactivation by SV40 T antigen.
- Overexpression of TBP did not relieve the inhibition between p53 and T antigen.
Conclusions:
- TBP may be a limiting factor for p53-mediated activation.
- p53 likely interacts with TBP to activate promoters containing p53-binding sites.
- The transcriptional antagonism between p53 and SV40 T antigen does not involve competition for TBP and may result from a direct inhibitory interaction between the proteins.
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