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Blood, 15 December 2003, Vol. 102, No. 13, pp. 4547-4554. Prepublished online as a Blood First Edition Paper on August 21, 2003; DOI 10.1182/blood-2003-01-0291. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0291v1 102/13/4547    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 Tamura, T. Articles by Ozato, K. Search for Related Content PubMed PubMed Citation Articles by Tamura, T. Articles by Ozato, K. Related Collections Hematopoiesis and Stem Cells Neoplasia Phagocytes Cell Cycle Oncogenes and Tumor Suppressors Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA ICSBP/IRF-8 inhibits mitogenic activity of p210 Bcr/Abl in differentiating myeloid progenitor cells Tomohiko Tamura, Hee Jeong Kong, Chainarong Tunyaplin, Hideki Tsujimura, Kathryn Calame, and Keiko Ozato From the Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development (NICHD), National Institutes of Health, Bethesda, MD; and Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, NY. Interferon consensus sequence binding protein/interferon regulatory factor 8 (ICSBP/IRF-8) is a transcription factor that controls myeloid cell development. ICSBP-/- mice develop a chronic myelogenous leukemia (CML)-like syndrome. Several observations on patients and mouse models have implicated ICSBP in the pathogenesis of CML. In this paper, we investigated whether ICSBP modulates the growth-promoting activity of Bcr/Abl, the causal oncoprotein for CML. When transformed with p210 Bcr/Abl, ICSBP-/- myeloid progenitor cells lost growth factor dependence and grew in the absence of granulocyte-macrophage colony-stimulating factor. When ICSBP was ectopically expressed, Bcr/Abl-transformed cells underwent complete growth arrest and differentiated into mature, functional macrophages without inhibiting the kinase activity of Bcr/Abl. Providing a mechanistic basis for the growth arrest, ICSBP markedly repressed c-Myc messenger RNA (mRNA)-expression, a downstream target of Bcr/Abl. A further analysis with the ICSBP/estrogen receptor chimera showed that ICSBP repression of c-Myc is indirect and is mediated by another gene(s). We identified Blimp-1 and METS/PE1, potent c-Myc repressors, as direct targets of ICSBP activated in these cells. Consistent with this, ectopic Blimp-1 repressed c-Myc expression and inhibited cell growth. These results indicate that ICSBP inhibits growth of Bcr/Abl-transformed myeloid progenitor cells by activating several genes that interfere with the c-Myc pathway. (Blood. 2003;102:4547-4554) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Alter-Koltunoff, S. Goren, J. Nousbeck, C. G. Feng, A. Sher, K. Ozato, A. Azriel, and B.-Z. Levi Innate Immunity to Intraphagosomal Pathogens Is Mediated by Interferon Regulatory Factor 8 (IRF-8) That Stimulates the Expression of Macrophage-specific Nramp1 through Antagonizing Repression by c-Myc J. Biol. Chem., February 1, 2008; 283(5): 2724 - 2733. [Abstract] [Full Text] [PDF] T. Tamura, P. Tailor, K. Yamaoka, H. J. Kong, H. Tsujimura, J. J. O'Shea, H. Singh, and K. Ozato IFN Regulatory Factor-4 and -8 Govern Dendritic Cell Subset Development and Their Functional Diversity J. Immunol., March 1, 2005; 174(5): 2573 - 2581. [Abstract] [Full Text] [PDF] J. Liu, X. Guan, T. Tamura, K. Ozato, and X. Ma Synergistic Activation of Interleukin-12 p35 Gene Transcription by Interferon Regulatory Factor-1 and Interferon Consensus Sequence-binding Protein J. Biol. Chem., December 31, 2004; 279(53): 55609 - 55617. [Abstract] [Full Text] [PDF]

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