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 |
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Rok vydání: | 2009 |
Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
Male Ribosomal Proteins Apoptosis Biology Pathogenesis Mice Downregulation and upregulation Pregnancy RNA interference Ribosomal protein Animals Humans Eye Abnormalities RNA Small Interfering Allele Hair Color ribosomal protein L24 cell cycle cell growth mouse embryonic development p53 checkpoint control Molecular Biology Mice Knockout Regulation of gene expression Gene Expression Regulation Developmental Articles Cell Biology Cell cycle Embryo Mammalian Phenotype Molecular biology Musculoskeletal Abnormalities Mice Inbred C57BL Survival Rate Cancer research Female RNA Interference Tumor Suppressor Protein p53 |
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 |
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