title: Regulation of kidney development by the Mdm2/Mdm4-p53 axis.
abstract: While p53 activity is required for tumour suppression, unconstrained p53 activity on the other hand is detrimental to the organism, resulting in inappropriate cellular death or proliferation defects. Unimpeded p53 activity is lethal in the developing embryo, underlining the need for maintaining a tight control on p53 activity during this period. The critical role of the negative regulators of p53, Mdm2 and Mdm4, in vertebrate development came to light by fatal disruption of embryogenesis that was observed with Mdm2 and Mdm4 gene deletions in mice. Embryonic lethality was rescued only by superimposing p53 removal. Here we summarize the contribution of the Mdm2/Mdm4-p53 axis that occurs at multiple steps of kidney development. Conditional, cell type-specific deletions reveal distinct functions of these proteins in renal morphogenesis. The severe impact on the renal phenotype from targeted gene deletions underscores the critical role played by the Mdm2/Mdm4-p53 nexus on nephrogenesis, and emphasizes the need to monitor patients with aberrations in this pathway for kidney function defects and associated cardiovascular dysfunction.
authors.affiliation: Department of Pediatrics, Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Samir
authors.initials: S
authors.lastname: El-Dahr
authors.affiliation: Department of Pediatrics, Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Hilliard
authors.affiliation: Department of Pediatrics, Section of Pediatric Nephrology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
authors.forename: Zubaida
authors.initials: Z
authors.lastname: Saifudeen
mesh_terms: D000818:Animals; D004734:Energy Metabolism; D006801:Humans; D007668:Kidney / Q000196:embryology* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Mdm2/MdmX/p53; embryonic; metanephric; nephrogenesis; progenitor