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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3186-3195. Prepublished online as a Blood First Edition Paper on July 10, 2003; DOI 10.1182/blood-2003-02-0567. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-02-0567v1 102/9/3186    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 Kobayashi, N. Articles by Yuo, A. Search for Related Content PubMed PubMed Citation Articles by Kobayashi, N. Articles by Yuo, A. Related Collections Hematopoiesis and Stem Cells Neoplasia Cell Cycle Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Granulocyte-macrophage colony-stimulating factor and interleukin-3 induce cell cycle progression through the synthesis of c-Myc protein by internal ribosome entry site–mediated translation via phosphatidylinositol 3-kinase pathway in human factor–dependent leukemic cells Norihiko Kobayashi, Kumiko Saeki, and Akira Yuo From the Department of Hematology, Research Institute, International Medical Center of Japan, Toyama, Shinjuku-ku, Tokyo, Japan; and Japan Society for the Promotion of Science, Tokyo. To investigate the roles of c-myc during hematopoietic proliferation induced by growth factors, we used factor-dependent human leukemic cell lines (MO7e and F36P) in which proliferation, cell cycle progression, and c-Myc expression were strictly regulated by granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3). In these cell lines, both c-myc mRNA and c-Myc protein stability were not affected by GM-CSF and IL-3, suggesting a regulation of c-Myc protein at the translational level. However, rapamycin, an inhibitor of cap-dependent translation, did not block c-myc induction by GM-CSF and IL-3. Thus, we studied the cap-independent translation, the internal ribosome entry site (IRES), during c-Myc protein synthesis using dicistronic reporter gene plasmids and found that GM-CSF and IL-3 activated c-myc IRES to initiate translation. c-myc IRES activation, c-Myc protein expression, and cell cycle progression were all blocked by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002. In another factor-dependent cell line, UT7, we observed the cell cycle progression and up-regulation of c-Myc protein, c-myc mRNA, and c-myc IRES simultaneously, which were all inhibited by LY294002. Results indicate that hematopoietic growth factors induce cell cycle progression via IRES-mediated translation of c-myc though the PI3K pathway in human factor–dependent leukemic cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Wall, G. Poortinga, K. M. Hannan, R. B. Pearson, R. D. Hannan, and G. A. McArthur Translational control of c-MYC by rapamycin promotes terminal myeloid differentiation Blood, September 15, 2008; 112(6): 2305 - 2317. [Abstract] [Full Text] [PDF] Z. Xiong, E. Liu, Y. Yan, R. T. Silver, F. Yang, I. H. Chen, Y. Chen, S. Verstovsek, H. Wang, J. Prchal, et al. An Unconventional Antigen Translated by a Novel Internal Ribosome Entry Site Elicits Antitumor Humoral Immune Reactions J. Immunol., October 1, 2006; 177(7): 4907 - 4916. [Abstract] [Full Text] [PDF] L. S. Haneline, H. White, F.-C. Yang, S. Chen, C. Orschell, R. Kapur, and D. A. Ingram Genetic reduction of class IA PI-3 kinase activity alters fetal hematopoiesis and competitive repopulating ability of hematopoietic stem cells in vivo Blood, February 15, 2006; 107(4): 1375 - 1382. [Abstract] [Full Text] [PDF] M. Kozak A second look at cellular mRNA sequences said to function as internal ribosome entry sites Nucleic Acids Res., November 28, 2005; 33(20): 6593 - 6602. [Abstract] [Full Text] [PDF]

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