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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4200-4208. Prepublished online as a Blood First Edition Paper on January 25, 2007; DOI 10.1182/blood-2006-08-044149. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-08-044149v1 109/10/4200    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 Koga, S. Articles by Minegishi, N. Search for Related Content PubMed PubMed Citation Articles by Koga, S. Articles by Minegishi, N. Related Collections Cell Cycle Gene Expression Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Cell-cycle–dependent oscillation of GATA2 expression in hematopoietic cells Shinichiro Koga1,2, Nobuhiro Yamaguchi1, Tomoko Abe1, Masayoshi Minegishi3, Shigeru Tsuchiya2, Masayuki Yamamoto4, and Naoko Minegishi1 1 Tohoku University Biomedical Engineering Research Organization, 2 Department of Pediatrics, Graduate School of Medicine, Tohoku University, Sendai, Japan; 3 Division of Blood Transfusion, Tohoku University Hospital, Sendai, Japan; 4 Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan In vitro manipulation of hematopoietic stem cells (HSCs) is a key issue in both transplantation therapy and regenerative medicine, and thus new methods are required to achieve HSC expansion with self-renewal. GATA2 is a transcription factor controlling pool size of HSCs. Of interest, continuous overexpression of GATA2 does not induce HSC proliferation. In this report, we demonstrate that GATA2 expression, in leukemic and normal hematopoietic cells, oscillates during the cell cycle, such that expression is high in S phase but low in G1/S and M phase. GATA2 binding to target Bcl-X gene also oscillates in accordance with GATA2 expression. Using a green fluorescent protein (GFP)–GATA2 fusion protein, we demonstrate cell-cycle–specific activity of proteasome-dependent degradation of GATA2. Immunoprecipitation/immunoblotting analysis demonstrated phosphorylation of GATA2 at cyclin-dependent kinase (Cdk)–consensus motifs, S/T0P+1, and interaction of GATA2 with Cdk2/cyclin A2–, Cdk2/cyclin A2–, and Cdk4/cyclin D1–phosphorylated GATA2 in vitro. Mutants in phosphorylation motifs exhibited altered expression profiles of GFP-GATA2 domain fusion proteins. These results indicate that GATA2 phosphorylation by Cdk/cyclin systems is responsible for the cell-cycle–dependent regulation of GATA2 expression, and suggest the possibility that a cell-cycle–specific "on-off" response of GATA2 expression may control hematopoietic-cell proliferation and survival. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. S. Viger, S. M. Guittot, M. Anttonen, D. B. Wilson, and M. Heikinheimo Role of the GATA Family of Transcription Factors in Endocrine Development, Function, and Disease Mol. Endocrinol., April 1, 2008; 22(4): 781 - 798. [Abstract] [Full Text] [PDF] C. Naujokat and T. Saric Concise Review: Role and Function of the Ubiquitin-Proteasome System in Mammalian Stem and Progenitor Cells Stem Cells, October 1, 2007; 25(10): 2408 - 2418. [Abstract] [Full Text] [PDF]

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