Hematopoietic Defects in rps29 Mutant Zebrafish Depend Upon p53 Activation

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Hematopoietic Defects in rps29 Mutant Zebrafish Depend Upon p53 Activation

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Title: Hematopoietic Defects in rps29 Mutant Zebrafish Depend Upon p53 Activation
Author: Taylor, Alison Marie; Humphries, Jessica M.; White, Richard; Murphey, Ryan D.; Burns, Caroline Erter; Zon, Leonard Ira

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Citation: Taylor, Alison M., Jessica M. Humphries, Richard M. White, Ryan D. Murphey, Caroline E. Burns, and Leonard I. Zon. 2012. Hematopoietic Defects in rps29 Mutant Zebrafish Depend Upon p53 Activation. Experimental Hematology 40, no. 3: 228–237.e5.
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Abstract: Disruption of ribosomal proteins is associated with hematopoietic phenotypes in cell culture and animal models. Mutations in ribosomal proteins are seen in patients with Diamond Black- fan anemia, a rare congenital disease characterized by red cell aplasia and distinctive cranio- facial anomalies. A zebrafish screen uncovered decreased hematopoietic stem cells in embryos with mutations in ribosomal protein rps29. Here, we determined that rps29L/L embryos also have red blood cell defects and increased apoptosis in the head. As the p53 pathway has been shown to play a role in other ribosomal protein mutants, we studied the genetic relationship of rps29 and p53. Transcriptional profiling revealed that genes upregulated in the rps29 mutant are enriched for genes upregulated by p53 after irradiation. p53 mutation near completely rescues the rps29 morphological and hematopoietic phenotypes, demonstrating that p53 medi- ates the effects of rps29 knockdown. We also identified neuronal gene orthopedia protein a (otpa) as one whose expression correlates with rps29 expression, suggesting that levels of expression of some genes are dependent on rps29 levels. Together, our studies demonstrate a role of p53 in mediating the cellular defects associated with rps29 and establish a role for rps29 and p53 in hematopoietic stem cells and red blood cell development.
Published Version: doi:10.1016/j.exphem.2011.11.007
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3310385/pdf/nihms-361719.pdf
Terms of Use: This article is made available under the terms and conditions applicable to Open Access Policy Articles, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#OAP
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12580119
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