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. Author manuscript; available in PMC: 2008 Dec 22.
Published in final edited form as: Am J Physiol Renal Physiol. 2008 Feb 20;294(6):F1273–F1278. doi: 10.1152/ajprenal.00562.2007

Figure 2. Role of p53 family in terminal nephron differentiation.

Figure 2

A. Terminal nephron differentiation is accompanied by p53 stabilization and enhanced DNA binding activity (J Clin Invest 109: 1021-1030, 2002). In the nephrogenic zone, p53 levels are kept low since p53 is repressed transcriptionally by Pax2 (EMBO J 14: 5638-45, 1995). The promoter of proliferating cell nuclear antigen (PCNA), which encodes a protein expressed in dividing cells and is necessary for cell cycle progression and DNA replication, is directly repressed by p53, and is therefore excluded from the differentiation zone (Am J Physiol Renal Physiol 283: F727-733, 2002). The genes encoding the CDK inhibitor, p21 (Cip1/Waf1) and KLF4, are direct targets of p53 (Cell 75: 817-825, 1993; J. Biol. Chem. 278: 2101-2105, 2003). In the differentiating zone, p53 binds to the promoters of terminal differentiation genes (also called renal function genes), including the bradykinin B2 receptor, aquaporin-2, and Na,K-ATPase a1. All of these genes have composite cis-regulatory elements for p53, KLF4 and CREB. B. Angiotensin II, acting via AT1 receptor-mediated signaling, stimulates the phosphorylation of CREB on Ser-133. The latter modification allows CREB to interact with p53 and the co-activator CBP. CBP acts as a bridging molecule with the basal transcriptional machinery as well as a histone acetyltransferase. The end result is enhanced BdkrB2 transcription (J Am Soc Nephrol 18: 1140-1149, 2007). C. p53 and its homologue p73 are capable of binding to the promoters of renal function genes and activating their expression. This function requires additional transcription factors including KLF4 or Foxi1. Fig. 2A is adapted with permission from Am J Physiol Renal Physiol 283: F727-733, 2002.