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Blood, 15 December 2008, Vol. 112, No. 13, pp. 5228-5237. Prepublished online as a Blood First Edition Paper on May 30, 2008; DOI 10.1182/blood-2008-01-132290. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-01-132290v1 112/13/5228    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Danilova, N. Articles by Lin, S. Search for Related Content PubMed PubMed Citation Articles by Danilova, N. Articles by Lin, S. Related Collections Hematopoiesis and Stem Cells Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family Nadia Danilova1, Kathleen M. Sakamoto2,3, and Shuo Lin1 1 Department of Molecular, Cell & Developmental Biology, University of California, Los Angeles (UCLA); 2 Division of Hematology/Oncology, Department of Pediatrics, Gwynne Hazen Cherry Memorial Laboratories and Mattel Children's Hospital, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA; and 3 Division of Biology, California Institute of Technology, Pasadena Mutations in several ribosomal proteins (RPs) lead to Diamond-Blackfan anemia (DBA), a syndrome characterized by defective erythropoiesis, congenital anomalies, and increased frequency of cancer. RPS19 is the most frequently mutated RP in DBA. RPS19 deficiency impairs ribosomal biogenesis, but how this leads to DBA or cancer remains unknown. We have found that rps19 deficiency in ze-brafish results in hematopoietic and developmental abnormalities resembling DBA. Our data suggest that the rps19-deficient phenotype is mediated by dysregulation of deltaNp63 and p53. During gastrulation, deltaNp63 is required for specification of nonneural ectoderm and its up-regulation suppresses neural differentiation, thus contributing to brain/craniofacial defects. In rps19-deficient embryos, deltaNp63 is induced in erythroid progenitors and may contribute to blood defects. We have shown that suppression of p53 and deltaNp63 alleviates the rps19-deficient phenotypes. Mutations in other ribosomal proteins, such as S8, S11, and S18, also lead to up-regulation of p53 pathway, suggesting it is a common response to ribosomal protein deficiency. Our finding provides new insights into pathogenesis of DBA. Ribosomal stress syndromes represent a broader spectrum of human congenital diseases caused by genotoxic stress; therefore, imbalance of p53 family members may become a new target for therapeutics. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Tefferi and J. W. Vardiman Myelodysplastic Syndromes N. Engl. J. Med., November 5, 2009; 361(19): 1872 - 1885. [Full Text] [PDF] L. M. McNamee and M. H. Brodsky p53-Independent Apoptosis Limits DNA Damage-Induced Aneuploidy Genetics, June 1, 2009; 182(2): 423 - 435. [Abstract] [Full Text] [PDF]

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