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Prepublished online as a Blood First Edition Paper on April 17, 2003; DOI 10.1182/blood-2003-02-0477. This Article Full Text (PDF) All Versions of this Article: 2003-02-0477v1 102/4/1267    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 Keeshan, K. Articles by Calabretta, B. Search for Related Content PubMed PubMed Citation Articles by Keeshan, K. Articles by Calabretta, B. Social Bookmarking                   What's this? Submitted February 12, 2003 Accepted April 4, 2003 The transcription activation function of C/EBP is required for induction of granulocytic differentiation Karen Keeshan, Giorgia Santilli, Francesca Corradini, Danilo Perrotti, and Bruno Calabretta* Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA Department of Biomedical Sciences, University of Modena and Reggio Emilia, Modena, Italy * Corresponding author; email: bruno.calabretta{at}mail.tju.edu. The CCAAT/enhancer binding protein-a (C/EBP)is a transcription factor required for differentiation of myeloid progenitors. In addition to specific DNA binding, C/EBP is also involved in protein-protein interactions, some of which (p21, Cdk2/Cdk4, E2F) appear to be required for inhibition of proliferation and possibly differentiation. To investigate the mechanisms of C/EBP-induced granulocytic differentiation, we generated C/EBP mutants reportedly defective in DNA binding, transactivation, Cdk2/Cdk4 and E2F interaction and assessed their effects in a myeloid precursor cell line, primary bone marrow and C/EBP knockout fetal liver precursor cells. We show here that the DNA-binding-deficient K298E mutant, the E2F-binding-deficient basic region mutant (BRM)-2 carrying the I294A and R297A substitutions, and the transactivation-deficient N-terminus truncated p30 mutant all fail to promote differentiation upon ectopic expression in myeloid precursor cells. By contrast, ectopic expression of the Cdk2/Cdk4-interaction deficient 177-191 mutant promotes differentiation and induces gene expression as effectively as wild-type C/EBP. Thus, the integrity of the transactivation and DNA binding domains, but not of the Cdk2/Cdk4 interaction region, is necessary for C/EBP-induced differentiation. Since the E2F-binding-deficient BRM-2 mutant interacted with E2F-1 but failed to activate gene expression, our results lend support to the hypothesis that activation of gene transcription is the determining factor in C/EBP-dependent differentiation. 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] J. S. Chang, R. Santhanam, R. Trotta, P. Neviani, A. M. Eiring, E. Briercheck, M. Ronchetti, D. C. Roy, B. Calabretta, M. A. Caligiuri, et al. 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