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A role for p53 in terminal epithelial cell differentiation
Zubaida Saifudeen1, Susana Dipp, Samir S El-Dahr
1Department of Pediatrics, SL-37, Tulane University Health Sciences Center, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
The Journal of Clinical Investigation
|April 17, 2002
Summary
The tumor suppressor protein p53 is essential for terminal differentiation of kidney epithelial cells. Loss of p53 disrupts renal function gene expression and causes kidney abnormalities.
Area of Science:
- Developmental Biology
- Molecular Biology
- Nephrology
Background:
- Terminal differentiation of renal epithelial cells is vital for kidney development and function.
- Failure in this differentiation process can lead to kidney dysplasia, cystogenesis, and cancer.
Purpose of the Study:
- To investigate the role of the tumor suppressor protein p53 in the terminal differentiation of renal epithelial cells.
- To determine if p53 influences the expression of renal function genes (RFGs).
Main Methods:
- Analysis of p53 and RFG expression in developing kidneys.
- Chromatin immunoprecipitation assays to assess p53 binding to RFG promoters.
- Studies using dominant-negative p53 mutants and p53-null mouse models.
- Evaluation of p73's ability to compensate for p53 loss.
Main Results:
- p53 is highly expressed in differentiating renal epithelial cells and co-localizes with RFGs.
- p53 directly binds to and activates the promoters of RFGs.
- Inhibition of p53 function impairs RFG expression.
- p53-null mice display aberrant renal phenotypes and disorganized RFG expression.
- The related protein p73 cannot functionally replace p53 in activating RFGs.
Conclusions:
- p53 is a key regulator promoting the biochemical and morphological differentiation of the renal epithelium.
- Aberrations in p53-mediated differentiation may contribute to nephron dysgenesis and dysfunction.
- p53 plays a critical role in maintaining kidney structure and function through regulating RFGs.
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