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Blood, 15 February 2005, Vol. 105, No. 4, pp. 1669-1677. Prepublished online as a Blood First Edition Paper on October 7, 2004; DOI 10.1182/blood-2004-06-2078. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-06-2078v1 105/4/1669    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 Lal, L. Articles by Platanias, L. C. Search for Related Content PubMed PubMed Citation Articles by Lal, L. Articles by Platanias, L. C. Related Collections Signal Transduction Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Activation of the p70 S6 kinase by all-trans-retinoic acid in acute promyelocytic leukemia cells Lakhvir Lal, Yongzhong Li, Jessica Smith, Antonella Sassano, Shahab Uddin, Simrit Parmar, Martin S. Tallman, Saverio Minucci, Nissim Hay, and Leonidas C. Platanias From the Robert H. Lurie Comprehensive Cancer Center and Division of Hematology-Oncology, Northwestern University School of Medicine and Lakeside VA Medical Center, and the Section of Hematology-Oncology, University of Chicago, IL; the Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago; and the Department of Experimental Oncology, European Institute of Oncology, Milan, Italy. Although the mechanisms by which all-trans-retinoic acid (RA) regulates gene transcription are well understood, very little is known on the signaling events regulating RA-dependent initiation of mRNA translation. We examined whether the mammalian target of rapamycin (mTOR)/p70 S6 kinase pathway is activated by RA. RA treatment of sensitive cell lines resulted in phosphorylation/activation of mTOR and downstream induction of p70 S6 kinase activity. Such phosphorylation/activation of p70 S6 kinase was inducible in primary acute promyelocytic leukemia (APL) blasts and RA-sensitive NB-4 cells, but was defective in an NB-4 variant cell line (NB-4.007/6) that is resistant to the biologic effects of RA. The RA-dependent activation of p70 S6 kinase was also phosphatidylinositol 3' kinase (PI3'K)-dependent, and resulted in downstream phosphorylation of the S6 ribosomal protein on Ser235/236 and Ser240/244, events important for initiation of translation for mRNAs with oligopyrimidine tracts in their 5' untranslated region. RA treatment of leukemia cells also resulted in an mTOR-mediated phosphorylation of the 4E-BP1 repressor of mRNA translation, to induce its deactivation and dissociation from the eukaryotic initiation factor-4E (eIF-4E) complex. Altogether, these findings provide evidence for the existence of a novel RA-activated cellular pathway that regulates cap-dependent translation, and strongly suggest that this cascade plays a role in the induction of retinoid responses in APL cells. (Blood. 2005;105:1669-1677) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Retinoid and growth factor receptor signaling in APL Jonathan D. Licht and Arthur Zelent Blood 2005 105: 1381-1382. [Full Text] [PDF] This article has been cited by other articles: T. Kogai, E. Ohashi, M. S. Jacobs, S. Sajid-Crockett, M. L. Fisher, Y. Kanamoto, and G. A. Brent Retinoic Acid Stimulation of the Sodium/Iodide Symporter in MCF-7 Breast Cancer Cells Is Meditated by the Insulin Growth Factor-I/Phosphatidylinositol 3-Kinase and p38 Mitogen-Activated Protein Kinase Signaling Pathways J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1884 - 1892. [Abstract] [Full Text] [PDF] B. Ozpolat, U. Akar, M. Steiner, I. Zorrilla-Calancha, M. Tirado-Gomez, N. Colburn, M. Danilenko, S. Kornblau, and G. Lopez Berestein Programmed Cell Death-4 Tumor Suppressor Protein Contributes to Retinoic Acid-Induced Terminal Granulocytic Differentiation of Human Myeloid Leukemia Cells Mol. Cancer Res., January 1, 2007; 5(1): 95 - 108. [Abstract] [Full Text] [PDF] P. Yoon, N. Giafis, J. Smith, H. Mears, E. Katsoulidis, A. Sassano, J. Altman, A. J. Redig, M. S. Tallman, and L. C. Platanias Activation of mammalian target of rapamycin and the p70 S6 kinase by arsenic trioxide in BCR-ABL-expressing cells. Mol. Cancer Ther., November 1, 2006; 5(11): 2815 - 2823. [Abstract] [Full Text] [PDF]

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