The p53 tumor suppressor causes congenital malformations in Rpl24-deficient mice and promotes their survival.
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.
Barkić
Martina
M
Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Braće Branchetta 20, 51000 Rijeka, Croatia.
Crnomarković
Sladana
S
Grabusić
Kristina
K
Bogetić
Ivana
I
Panić
Linda
L
Tamarut
Sanda
S
Cokarić
Maja
M
Jerić
Ines
I
Vidak
Sandra
S
Volarević
Sinisa
S
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*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D034741:RNA, Small Interfering; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; C036298:ribosomal protein L24