title: The p53 tumor suppressor causes congenital malformations in Rpl24-deficient mice and promotes their survival.
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.
authors.affiliation: Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
authors.forename: Martina
authors.initials: M
authors.lastname: Barkić
authors.forename: Sladana
authors.initials: S
authors.lastname: Crnomarković
authors.forename: Kristina
authors.initials: K
authors.lastname: Grabusić
authors.forename: Ivana
authors.initials: I
authors.lastname: Bogetić
authors.forename: Linda
authors.initials: L
authors.lastname: Panić
authors.forename: Sanda
authors.initials: S
authors.lastname: Tamarut
authors.forename: Maja
authors.initials: M
authors.lastname: Cokarić
authors.forename: Ines
authors.initials: I
authors.lastname: Jerić
authors.forename: Sandra
authors.initials: S
authors.lastname: Vidak
authors.forename: Sinisa
authors.initials: S
authors.lastname: Volarević
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000502:physiology; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006200:Hair Color / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009139:Musculoskeletal Abnormalities / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; C036298:ribosomal protein L24