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Blood, 15 July 2008, Vol. 112, No. 2, pp. 320-329. Prepublished online as a Blood First Edition Paper on March 13, 2008; DOI 10.1182/blood-2007-11-126300. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-11-126300v1 112/2/320    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 Waning, D. L. Articles by Chun, K. T. Search for Related Content PubMed PubMed Citation Articles by Waning, D. L. Articles by Chun, K. T. Related Collections Hematopoiesis and Stem Cells Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Cul4A is required for hematopoietic cell viability and its deficiency leads to apoptosis David L. Waning1, Binghui Li1, Nan Jia1, Yahaira Naaldijk1,2, W. Scott Goebel1, Harm HogenEsch3, and Kristin T. Chun1,2 1 Herman B Wells Center for Pediatric Research, Section of Pediatric Hematology/Oncology, Department of Pediatrics, 2 Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis; and 3 Department of Comparative Pathobiology, Purdue University, West Lafayette, IN In vitro studies indicate that Cul4A ubiquitin ligases target for ubiquitin-mediated proteolysis regulators of cell-cycle progression, apoptosis, development, and DNA repair. In hematopoietic cell lines, studies by our group and others showed that Cul4A ligases regulate proliferation and differentiation in maturing myeloid and erythroid cells. In vivo, Cul4A-deficient embryos die in utero. Cul4A haploinsufficient mice are viable but have fewer erythroid and primitive myeloid progenitors. Yet, little more is known about Cul4A function in vivo. To examine Cul4A function in adults, we generated mice with interferon-inducible deletion of Cul4A. Cul4A deficiency resulted in DNA damage and apoptosis of rapidly dividing cells, and mutant mice died within 3 to 10 days after induction with dramatic atrophy of the intestinal villi, bone marrow, and spleen, and with hematopoietic failure. Cul4A deletion in vivo specifically increased cellular levels of the Cul4A ligase targets Cdt1 and p27Kip1 but not other known targets. Bone marrow transplantation studies with Cul4A deletion in engrafted cells specifically isolated analysis of Cul4A function to hematopoietic cells and resulted in hematopoietic failure. These recipients died within 9 to 11 days, demonstrating that in hematopoietic cells, Cul4A is essential for survival. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Culling for survival André Catic Blood 2008 112: 211-212. [Full Text] [PDF] This article has been cited by other articles: Y. Zou, J. Mi, J. Cui, D. Lu, X. Zhang, C. Guo, G. Gao, Q. Liu, B. Chen, C. Shao, et al. Characterization of Nuclear Localization Signal in the N Terminus of CUL4B and Its Essential Role in Cyclin E Degradation and Cell Cycle Progression J. Biol. Chem., November 27, 2009; 284(48): 33320 - 33332. [Abstract] [Full Text] [PDF]

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