The P53 Tumor Suppressor Causes Congenital Malformations in Rpl24-deficient Mice and Promotes Their Survival

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2009 Mar 11

PMID 19273598

Citations 61

Authors

Martina Barkic

Sladana Crnomarkovic

Kristina Grabusic

Ivana Bogetic

Linda Panic

Sanda Tamarut

Maja Cokaric

Ines Jeric

Sandra Vidak

Sinisa Volarevic

Affiliations

Soon will be listed here.

Abstract

Hypomorphic mutation in one allele of ribosomal protein l24 gene (Rpl24) is responsible for the Belly Spot and Tail (Bst) mouse, which suffers from defects of the eye, skeleton, and coat pigmentation. It has been hypothesized that these pathological manifestations result exclusively from faulty protein synthesis. We demonstrate here that upregulation of the p53 tumor suppressor during the restricted period of embryonic development significantly contributes to the Bst phenotype. However, in the absence of p53 a large majority of Rpl24(Bst/+) embryos die. We showed that p53 promotes survival of these mice via p21-dependent mechanism. Our results imply that activation of a p53-dependent checkpoint mechanism in response to various ribosomal protein deficiencies might also play a role in the pathogenesis of congenital malformations in humans.

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