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Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-02-0479. This Article Full Text (PDF) All Versions of this Article: 2003-02-0479v1 102/9/3163    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 Johansen, L. M Articles by Tenen, D. G Search for Related Content PubMed PubMed Citation Articles by Johansen, L. M Articles by Tenen, D. G Social Bookmarking                   What's this? Submitted February 13, 2003 Accepted June 28, 2003 The amino terminal and E2F interaction domains are critical for C/EBP-mediated induction of granulopoietic development of hematopoietic cells Lisa M Johansen, Francesco D'Alo', Erik A Nelson, Hanna S Radomska, Erica K Evans, Pu Zhang, Claus Nerlov, and Daniel G Tenen* Hematology/Oncology Division, Harvard Institutes of Medicine, Harvard Medical School, Boston, MA, USA European Molecular Biology Laboratory, Monterotondo, Italy * Corresponding author; email: dtenen{at}bidmc.harvard.edu. The transcription factor C/EBP is critical for granulopoiesis. Disruption of this gene in the mouse leads to an early block in myeloid differentiation, and disruption by mutation or other mechanisms has been implicated in the pathogenesis of human Acute Myelogenous Leukemia (AML). Previous studies have implicated a number of critical C/EBP target genes in granulopoiesis, but no systematic structure-functional analysis has been undertaken to identify the mechanisms involved in C/EBP mediated granulocyte differentiation. Here we demonstrate by that loss of either of two key regions result in disruption of C/EBP granulocytic differentiation function: an amino terminal part of the C/EBP transactivation domain, and specific residues residing on the non-DNA binding face of the basic domain. Mutation of either region results in loss of the ability of C/EBP to inhibit E2F function and down-regulate c-Myc, but only mutation of the basic domain residues results in loss of physical interaction of C/EBP with E2F. In contrast, while a mutant which has lost of the amino terminal activation domain retains the ability to interact with E2F, this mutant fails to bind C/EBP target sites efficiently, activate C/EBP target genes, and is also defective in inhibition of E2F activity. These results further emphasize the importance of inhibition of proliferative pathways in granulopoiesis, and demonstrate that several regions of the C/EBP protein are involved in this mechanism. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. R. Soliera, M. R. Lidonnici, G. Ferrari-Amorotti, M. Prisco, Y. Zhang, R. V. Martinez, N. J. Donato, and B. Calabretta Transcriptional repression of c-Myb and GATA-2 is involved in the biologic effects of C/EBP{alpha} in p210BCR/ABL-expressing cells Blood, September 1, 2008; 112(5): 1942 - 1950. [Abstract] [Full Text] [PDF] S. Koschmieder, F. D'Alo, H. Radomska, C. Schoneich, J. S. Chang, M. Konopleva, S. Kobayashi, E. Levantini, N. Suh, A. Di Ruscio, et al. CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer binding protein alpha Blood, November 15, 2007; 110(10): 3695 - 3705. 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