The p53 Tumor Suppressor Causes Congenital Malformations in Rpl24-Deficient Mice and Promotes Their Survival

Autor: Maja Cokarić, Kristina Grabušić, Martina Barkić, Sanda Tamarut, Siniša Volarević, Ines Jerić, Ivana Bogetić, Linda Panić, Sandra Vidak, Slađana Crnomarković
Rok vydání: 2009
Předmět:
Zdroj: Molecular and Cellular Biology. 29:2489-2504
ISSN: 1098-5549
DOI: 10.1128/mcb.01588-08
Popis: 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.
Databáze: OpenAIRE