The master regulators Myc and p53 cellular signaling and functions in polycystic kidney disease.

Cellular Signalling
Almira Kurbegovic, Marie Trudel

Abstract

The transcription factors Myc and p53 associated with oncogenesis play determinant roles in a human genetic disorder, autosomal dominant polycystic kidney disease (ADPKD), that was coined early in ADPKD etiology a «neoplasia in disguise ». These factors are interdependent master cell regulators of major biological processes including proliferation, apoptosis, cell growth, metabolism, inflammation, fibrosis and differentiation that are all modulated in ADPKD. Myc and p53 proteins evolved to respond and carry out overlapping functions via opposing mechanisms of action. Studies in human ADPKD kidneys, caused by mutations in the PKD1 or PKD2 genes, reveal reduced p53 expression and high expression of Myc in the cystic tubular epithelium. Myc and p53 via direct interaction act respectively, as transcriptional activator and repressor of PKD1 gene expression, consistent with increased renal PKD1 levels in ADPKD. Mouse models generated by Pkd1 and Pkd2 gene dosage dysregulation reproduce renal cystogenesis with activation of Myc expression and numerous signaling pathways, strikingly similar to those determined in human ADPKD. In fact, upregulation of renal Myc expression is also detected in virtually all non-orthologous animal models o...Continue Reading

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Citations

Aug 23, 2020·Biomedicines·Shoib Sarwar SiddiquiCijo George Vazhappilly
Apr 15, 2021·Cell Metabolism·Harini RamalingamVishal Patel
Jun 15, 2021·Frontiers in Bioengineering and Biotechnology·Sarah MyramSylvie Coscoy

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