Aberrations in proliferation and differentiation in the developing kidney often result in renal dysplasia or cancer. Therefore, a clear understanding of the molecular mechanisms of normal renal differentiation is a prerequisite to understanding the molecular basis of kidney disease. There is evidence linking p53 to renal cell differentiation. The goal of this project is to test the hypothesis that p53 function in the kidney is essential for normal terminal differentiation of renal epithelia. Cells that are terminally differentiated have not only ceased proliferation but have also acquired functional characteristics. The first specific aim will show that p53 promotes the expression of several renal function genes that are expressed in terminally differentiated epithelia. The second specific aim will examine the changes in expression and distribution patterns of renal function proteins in the absence of p53 function, either by using p53-null mice or generating transgenic mice that lack the p53 response element in the promoter of a renal function gene. The results of this work will provide information on what determines terminal renal differentiation. In addition, these data will advance our understanding of the role the tumor suppressor p53 in kidney development.
| Saifudeen, Zubaida; Dipp, Susana; Fan, Hao et al. (2005) Combinatorial control of the bradykinin B2 receptor promoter by p53, CREB, KLF-4, and CBP: implications for terminal nephron differentiation. Am J Physiol Renal Physiol 288:F899-909 |
| Marks, Jessica; Saifudeen, Zubaida; Dipp, Susana et al. (2003) Two functionally divergent p53-responsive elements in the rat bradykinin B2 receptor promoter. J Biol Chem 278:34158-66 |
| Saifudeen, Zubaida; Dipp, Susana; El-Dahr, Samir S (2002) A role for p53 in terminal epithelial cell differentiation. J Clin Invest 109:1021-30 |
| Saifudeen, Zubaida; Marks, Jessica; Du, Hong et al. (2002) Spatial repression of PCNA by p53 during kidney development. Am J Physiol Renal Physiol 283:F727-33 |
