SEARCH:   Advanced

Blood, 1 November 2003, Vol. 102, No. 9, pp. 3163-3171. Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-02-0479. This Article Full Text 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 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 D'Alo', F. Articles by Tenen, D. G. Search for Related Content PubMed PubMed Citation Articles by D'Alo', F. Articles by Tenen, D. G. Related Collections Gene Expression Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS The amino terminal and E2F interaction domains are critical for C/EBP-mediated induction of granulopoietic development of hematopoietic cells Francesco D'Alo', Lisa M. Johansen, Erik A. Nelson, Hanna S. Radomska, Erica K. Evans, Pu Zhang, Claus Nerlov, and Daniel G. Tenen From the Hematology/Oncology Division, Harvard Institutes of Medicine, Harvard Medical School, Boston, MA; and European Molecular Biology Laboratory, Monterotondo, Italy. The transcription factor C/EBP (CCAAT/enhancer binding protein ) is critical for granulopoiesis. Gene disruption in mice blocks early granulocyte differentiation and disruption of C/EBP function has been implicated in human acute myeloid leukemia (AML), but no systematic structure-function analysis has been undertaken to identify the mechanisms involved in C/EBP-mediated granulocyte differentiation. Here we demonstrate that loss of either of 2 key regions results in disruption of C/EBP granulocytic development: the amino terminus and specific residues residing on the non-DNA binding face of the basic region. Mutation of either results in loss of C/EBP inhibition of E2F and down-regulation of c-Myc, but only mutation of the basic region results in loss of physical interaction with E2F. In contrast, while the amino terminal mutant retains the ability to interact with E2F, this mutant fails to bind a C/EBP site efficiently, fails to 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. [Abstract] [Full Text] [PDF] M. Geletu, M. Y. Balkhi, A. A. Peer Zada, M. Christopeit, J. A. Pulikkan, A. K. Trivedi, D. G. Tenen, and G. Behre Target proteins of C/EBP{alpha}p30 in AML: C/EBP{alpha}p30 enhances sumoylation of C/EBP{alpha}p42 via up-regulation of Ubc9 Blood, November 1, 2007; 110(9): 3301 - 3309. [Abstract] [Full Text] [PDF] J. Cheng, D. V. Yu, J.-H. Zhou, and D. J. Shapiro Tamoxifen Induction of CCAAT Enhancer-binding Protein {alpha} Is Required for Tamoxifen-induced Apoptosis J. Biol. Chem., October 19, 2007; 282(42): 30535 - 30543. [Abstract] [Full Text] [PDF] Y.-J. Lee, L. C. Jones, N. A. Timchenko, D. Perrotti, D. G. Tenen, and S. C. Kogan CCAAT/enhancer binding proteins alpha and epsilon cooperate with all-trans retinoic acid in therapy but differ in their antileukemic activities Blood, October 1, 2006; 108(7): 2416 - 2419. [Abstract] [Full Text] [PDF] G. Ferrari-Amorotti, K. Keeshan, M. Zattoni, C. Guerzoni, G. Iotti, S. Cattelani, N. J. Donato, and B. Calabretta Leukemogenesis induced by wild-type and STI571-resistant BCR/ABL is potently suppressed by C/EBP{alpha} Blood, August 15, 2006; 108(4): 1353 - 1362. [Abstract] [Full Text] [PDF] A. T. J. Wierenga, H. Schepers, M. A. S. Moore, E. Vellenga, and J. J. Schuringa STAT5-induced self-renewal and impaired myelopoiesis of human hematopoietic stem/progenitor cells involves down-modulation of C/EBP{alpha} Blood, June 1, 2006; 107(11): 4326 - 4333. [Abstract] [Full Text] [PDF] K. Wagner, P. Zhang, F. Rosenbauer, B. Drescher, S. Kobayashi, H. S. Radomska, J. L. Kutok, D. G. Gilliland, J. Krauter, and D. G. Tenen Absence of the transcription factor CCAAT enhancer binding protein {alpha} results in loss of myeloid identity in bcr/abl-induced malignancy PNAS, April 18, 2006; 103(16): 6338 - 6343. [Abstract] [Full Text] [PDF] H. S. Radomska, D. S. Basseres, R. Zheng, P. Zhang, T. Dayaram, Y. Yamamoto, D. W. Sternberg, N. Lokker, N. A. Giese, S. K. Bohlander, et al. Block of C/EBP{alpha} function by phosphorylation in acute myeloid leukemia with FLT3 activating mutations J. Exp. Med., February 21, 2006; 203(2): 371 - 381. [Abstract] [Full Text] [PDF] B. T. Porse, T. A. Pedersen, M. S. Hasemann, M. B. Schuster, P. Kirstetter, T. Luedde, I. Damgaard, E. Kurz, C. K. Schjerling, and C. Nerlov The Proline-Histidine-Rich CDK2/CDK4 Interaction Region of C/EBP{alpha} Is Dispensable for C/EBP{alpha}-Mediated Growth Regulation In Vivo Mol. Cell. Biol., February 1, 2006; 26(3): 1028 - 1037. [Abstract] [Full Text] [PDF] B. T. Porse, D. Bryder, K. Theilgaard-Monch, M. S. Hasemann, K. Anderson, I. Damgaard, S. E. W. Jacobsen, and C. Nerlov Loss of C/EBP{alpha} cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage J. Exp. Med., July 5, 2005; 202(1): 85 - 96. [Abstract] [Full Text] [PDF] E. Parrella, M. Gianni', V. Cecconi, E. Nigro, M. M. Barzago, A. Rambaldi, C. Rochette-Egly, M. Terao, and E. Garattini Phosphodiesterase IV Inhibition by Piclamilast Potentiates the Cytodifferentiating Action of Retinoids in Myeloid Leukemia Cells: CROSS-TALK BETWEEN THE cAMP AND THE RETINOIC ACID SIGNALING PATHWAYS J. Biol. Chem., October 1, 2004; 279(40): 42026 - 42040. [Abstract] [Full Text] [PDF] M. Schwieger, J. Lohler, M. Fischer, U. Herwig, D. G. Tenen, and C. Stocking A dominant-negative mutant of C/EBP{alpha}, associated with acute myeloid leukemias, inhibits differentiation of myeloid and erythroid progenitors of man but not mouse Blood, April 1, 2004; 103(7): 2744 - 2752. [Abstract] [Full Text] [PDF] D. Perrotti, G. Marcucci, and M. A. Caligiuri Loss of C/EBP{alpha} and Favorable Prognosis of Acute Myeloid Leukemias: A Biological Paradox J. Clin. Oncol., February 15, 2004; 22(4): 582 - 584. [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020