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Blood, 15 March 2007, Vol. 109, No. 6, pp. 2630-2633. Prepublished online as a Blood First Edition Paper on November 14, 2006; DOI 10.1182/blood-2006-03-013656. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2006-03-013656v1 109/6/2630    most recent Alert me when this article is cited Alert me if a correction is posted 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 Maetens, M. Articles by Marine, J.-C. Search for Related Content PubMed PubMed Citation Articles by Maetens, M. Articles by Marine, J.-C. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 29, 2006 Accepted November 6, 2006 Distinct Roles of Mdm2 and Mdm4 in Red Cell Production Marion Maetens, Gilles Doumont, Sarah De Clercq, Sarah Francoz, Pascal Froment, Eric Bellefroid, Ursula Klingmuller, Guillermina Lozano, and Jean-Christophe Marine* Flanders Interuniversity Institute for Biotechnology (VIB), University of Ghent, Ghent, Belgium Laboratory of Molecular Embryology, Free University of Brussels (ULB-IBMM), Gosselies, Belgium German Cancer Research Center, Heidelberg, Germany The University of Texas MD Anderson Cancer Center, Houston, TX, United States * Corresponding author; email: chris.marine{at}dmbr.ugent.be. Mdm2 and Mdm4 are critical negative regulators of the p53 tumor suppressor. mdm4-null mutants are severely anemic and exhibit impaired proliferation of the fetal liver erythroid lineage cells. This phenotype may indicate a cell intrinsic function of Mdm4 in erythropoiesis. In contrast, red blood cell count was nearly normal in mice engineered to express low levels of Mdm2, suggesting that Mdm2 might be dispensable for red cell production. Here, we further explore the tissue-specific functions of Mdm2 and Mdm4 in the erythroid lineage by inter-crossing conditional mdm4 and mdm2 alleles to an erythroid specific Cre (Er-GFP-Cre) knock-in allele. Our data show that Mdm2 is required for rescuing erythroid progenitors from p53-mediated apoptosis during primitive erythropoiesis. In contrast, Mdm4 is required only for the high erythropoietic rate during embryonic definitive erythropoiesis. Thus, in this particular cellular context, Mdm4 only contributes to p53 regulation at a specific phase of the differentiation program. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. D. Trainor, C. Mas, P. Archambault, P. Di Lello, and J. G. Omichinski GATA-1 associates with and inhibits p53 Blood, July 2, 2009; 114(1): 165 - 173. [Abstract] [Full Text] [PDF] C. Prives and E. White Does control of mutant p53 by Mdm2 complicate cancer therapy? Genes & Dev., May 15, 2008; 22(10): 1259 - 1264. [Abstract] [Full Text] [PDF] V. G. Sankaran, S. H. Orkin,, and C. R. Walkley Rb intrinsically promotes erythropoiesis by coupling cell cycle exit with mitochondrial biogenesis Genes & Dev., February 15, 2008; 22(4): 463 - 475. [Abstract] [Full Text] [PDF]

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