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Two functionally divergent p53-responsive elements in the rat bradykinin B2 receptor promoter
Jessica Marks1, Zubaida Saifudeen, Susana Dipp
1Department of Pediatrics, Section of Pediatric Nephrology, Tulane University Health Sciences Center, New Orleans, Louisiana 70112, USA.
The Journal of Biological Chemistry
|June 7, 2003
Summary
This study reveals the tumor suppressor protein p53 can both activate and repress gene transcription from the same promoter. Researchers identified specific DNA elements controlling these opposing functions in the bradykinin B2 receptor gene.
Area of Science:
- Molecular Biology
- Gene Regulation
- Transcription Factor Function
Background:
- The tumor suppressor protein p53 is known to act as both a transcriptional activator and repressor.
- However, examples of a single target promoter containing both activating and repressing p53 elements have been lacking.
- Previous research identified two p53 response elements (P1 and P2) in the rat bradykinin B2 receptor promoter.
Purpose of the Study:
- To investigate the distinct roles of P1 and P2 in p53-mediated transcriptional regulation.
- To determine if these elements function as activators or repressors and how their sequence and genomic context influence their activity.
- To elucidate the mechanisms underlying p53's dual function within a single promoter.
Main Methods:
- Site-directed mutagenesis and DNA sequence manipulation to alter P1 and P2 elements.
- Reporter gene assays to measure transcriptional activity.
- Deletion and relocation of response elements within the promoter and to heterologous promoters.
- Gel shift assays to assess protein-DNA interactions.
Main Results:
- P1 acts as a bona fide p53-activating element, essential for p53-mediated activation, and retains its function upon relocation.
- P2 functions as a repressing element, and its deletion enhances P1-mediated activation.
- P2-mediated repression is sequence- and context-dependent, convertible to activation by sequence changes or relocation.
- p53 may compete with other activators for binding at the P2 element, contributing to repression.
Conclusions:
- This study presents a rare example of a single transcription factor, p53, exhibiting both activating and repressing functions dependent on DNA sequence and genomic context.
- The interplay between P1 and P2 elements is crucial for regulating bradykinin B2 receptor gene expression.
- These findings offer insights into the complex regulatory mechanisms of gene expression under stress and during development.