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14:57
Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
p53 inactivation upregulates p73 expression through E2F-1 mediated transcription
Chaitali Tophkhane1, Shi-He Yang, Yunbo Jiang
1Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
Plos One
|September 7, 2012
Summary
p53 inactivation upregulates the tumor suppressor p73 (p73) through E2F-1 transcriptional regulation, suggesting a compensatory mechanism in cancer. This finding highlights the importance of p53 status in predicting cancer prognosis.
Area of Science:
- Molecular Biology
- Cancer Research
- Genetics
Background:
- p73 overexpression is linked to increased apoptosis but high-grade malignancy in cancers.
- The reasons for p73 overexpression and its function in breast cancer remain unclear.
- Understanding the p53-p73 relationship is crucial for cancer therapy.
Purpose of the Study:
- To investigate how p53 inactivation affects p73 expression.
- To elucidate the regulatory mechanisms of p73 upregulation upon p53 loss.
- To explore the role of E2F-1 and p21 in this process.
Main Methods:
- Utilized cell lines with p53 inactivation (siRNA, mutations, knockout).
- Analyzed p73 protein and mRNA levels.
- Performed promoter activity assays and chromatin immunoprecipitation (ChIP).
Main Results:
- p53 inactivation significantly increased TAp73 protein and mRNA levels.
- p73 upregulation was primarily transcriptional, mediated by E2F-1 binding to the TAp73 promoter.
- p21 was identified as a mediator in the p53-E2F crosstalk regulating p73 transcription.
Conclusions:
- p53 inactivation upregulates TAp73 via E2F-1-mediated transcriptional control.
- This upregulation may represent an intrinsic survival mechanism against p53 loss.
- Further research into p53-p73 correlation is vital for cancer prognosis and treatment.
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