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Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects.

ABSTRACT: Mutations in genes encoding ribosomal proteins cause the Minute phenotype in Drosophila and mice, and Diamond-Blackfan syndrome in humans. Here we report two mouse dark skin (Dsk) loci caused by mutations in Rps19 (ribosomal protein S19) and Rps20 (ribosomal protein S20). We identify a common pathophysiologic program in which p53 stabilization stimulates Kit ligand expression, and, consequently, epidermal melanocytosis via a paracrine mechanism. Accumulation of p53 also causes reduced body size and erythrocyte count. These results provide a mechanistic explanation for the diverse collection of phenotypes that accompany reduced dosage of genes encoding ribosomal proteins, and have implications for understanding normal human variation and human disease.

SUBMITTER: McGowan KA

PROVIDER: S-EPMC3979291 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects.

McGowan Kelly A KA Li Jun Z JZ Park Christopher Y CY Beaudry Veronica V Tabor Holly K HK Sabnis Amit J AJ Zhang Weibin W Fuchs Helmut H de Angelis Martin Hrabé MH Myers Richard M RM Attardi Laura D LD Barsh Gregory S GS

Nature genetics 20080720 8

Mutations in genes encoding ribosomal proteins cause the Minute phenotype in Drosophila and mice, and Diamond-Blackfan syndrome in humans. Here we report two mouse dark skin (Dsk) loci caused by mutations in Rps19 (ribosomal protein S19) and Rps20 (ribosomal protein S20). We identify a common pathophysiologic program in which p53 stabilization stimulates Kit ligand expression, and, consequently, epidermal melanocytosis via a paracrine mechanism. Accumulation of p53 also causes reduced body size ...[more]

PMID: 18641651

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