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Molecular and Cellular Biology, May 2009, p. 2489-2504, Vol. 29, No. 10
0270-7306/09/$08.00+0     doi:10.1128/MCB.01588-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The p53 Tumor Suppressor Causes Congenital Malformations in Rpl24-Deficient Mice and Promotes Their Survival {triangledown} ,{ddagger}

Martina Barkic,{dagger} Sladana Crnomarkovic,{dagger} Kristina Grabusic, Ivana Bogetic, Linda Panic, Sanda Tamarut, Maja Cokaric, Ines Jeric, Sandra Vidak, and Sinisa Volarevic*

Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Brace Branchetta 20, 51000 Rijeka, Croatia

Received 9 October 2008/ Returned for modification 18 November 2008/ Accepted 23 February 2009

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 Rpl24Bst/+ 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.

* Corresponding author. Mailing address: Department of Molecular Medicine and Biotechnology, School of Medicine, University of Rijeka, Brace Branchetta 20, 51000 Rijeka, Croatia. Phone: 385 51-651-120. Fax: 385 51-651-197. E-mail: vsinisa{at}medri.hr

{triangledown} Published ahead of print on 9 March 2009.

{ddagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{dagger} M.B. and S.C. contributed equally to this study.

Molecular and Cellular Biology, May 2009, p. 2489-2504, Vol. 29, No. 10
0270-7306/09/$08.00+0     doi:10.1128/MCB.01588-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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