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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2305-2317. Prepublished online as a Blood First Edition Paper on July 11, 2008; DOI 10.1182/blood-2007-09-111856. This Article Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-09-111856v1 112/6/2305    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 Wall, M. Articles by McArthur, G. A Search for Related Content PubMed PubMed Citation Articles by Wall, M. Articles by McArthur, G. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 28, 2007 Accepted February 26, 2008 Translational control of c-MYC by rapamycin promotes terminal myeloid differentiation Meaghan Wall, Gretchen Poortinga, Katherine M Hannan, Richard B Pearson, Ross D Hannan, and Grant A McArthur* Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, Victoria, Australia Division of Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, Australia Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia Division of Haematology/Medical Oncology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia * Corresponding author; email: grant.mcarthur{at}petermac.org. c-MYC inhibits differentiation and regulates the process by which cells acquire biomass, cell growth. Downregulation of c-MYC, reduced cell growth and decreased activity of the PI3K/AKT/mTORC1 signal transduction pathway are features of the terminal differentiation of committed myeloid precursors to polymorphonuclear neutrophils. Since mTORC1 regulates growth we hypothesised that pharmacological inhibition of mTORC1 by rapamycin may reverse the phenotypic effects of c-MYC. Here we show that granulocytes blocked in their ability to differentiate by enforced expression of c-MYC can be induced to differentiate by reducing exogenous c-MYC expression through rapamycin treatment. Rapamycin also reduced expression of endogenous c-MYC and resulted in enhanced retinoid-induced differentiation. Total cellular c-Myc mRNA and c-MYC protein stability were unchanged by rapamycin however the amount of c-Myc mRNA associated with polysomes was reduced. Therefore rapamycin limited expression of c-MYC by inhibiting c-Myc mRNA translation. These findings suggest that mTORC1 could be targeted to promote terminal differentiation in myeloid malignancies characterised by dysregulated expression of c-MYC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Liu, J. N. Rao, T. Zou, L. Xiao, P.-Y. Wang, D. J. Turner, M. Gorospe, and J.-Y. Wang Polyamines Regulate c-Myc Translation through Chk2-dependent HuR Phosphorylation Mol. Biol. Cell, December 1, 2009; 20(23): 4885 - 4898. [Abstract] [Full Text] [PDF]

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