Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 5023K) PPT slides of all figures Supplemental Material Index Related biobytes podcast Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ramírez-Valle, F. Articles by Schneider, R. J. Search for Related Content PubMed PubMed Citation Articles by Ramírez-Valle, F. Articles by Schneider, R. J. Related Collections Related In this Issue article Social Bookmarking                            What's this?

eIF4GI links nutrient sensing by mTOR to cell proliferation and inhibition of autophagy

¹ Department of Microbiology, ² Department of Pathology, and ³ Department of Radiation Oncology, New York University School of Medicine, New York, NY 10016

Correspondence to Robert J. Schneider: schner01{at}med.nyu.edu

Translation initiation factors have complex functions in cells that are not yet understood. We show that depletion of initiation factor eIF4GI only modestly reduces overall protein synthesis in cells, but phenocopies nutrient starvation or inhibition of protein kinase mTOR, a key nutrient sensor. eIF4GI depletion impairs cell proliferation, bioenergetics, and mitochondrial activity, thereby promoting autophagy. Translation of mRNAs involved in cell growth, proliferation, and bioenergetics were selectively inhibited by reduction of eIF4GI, as was the mRNA encoding Skp2 that inhibits p27, whereas catabolic pathway factors were increased. Depletion or overexpression of other eIF4G family members did not recapitulate these results. The majority of mRNAs that were translationally impaired with eIF4GI depletion were excluded from polyribosomes due to the presence of multiple upstream open reading frames and low mRNA abundance. These results suggest that the high levels of eIF4GI observed in many breast cancers might act to specifically increase proliferation, prevent autophagy, and release tumor cells from control by nutrient sensing.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related In this Issue article

An eIF for proliferation

Nicole LeBrasseur
J. Cell Biol. 2008 181: 175. [Full Text] [PDF]

This article has been cited by other articles:

• Chresta, C. M., Davies, B. R., Hickson, I., Harding, T., Cosulich, S., Critchlow, S. E., Vincent, J. P., Ellston, R., Jones, D., Sini, P., James, D., Howard, Z., Dudley, P., Hughes, G., Smith, L., Maguire, S., Hummersone, M., Malagu, K., Menear, K., Jenkins, R., Jacobsen, M., Smith, G. C.M., Guichard, S., Pass, M. (2010). AZD8055 Is a Potent, Selective, and Orally Bioavailable ATP-Competitive Mammalian Target of Rapamycin Kinase Inhibitor with In vitro and In vivo Antitumor Activity. Cancer Res. 70: 288-298 [Abstract] [Full Text]  
• Parsyan, A., Shahbazian, D., Martineau, Y., Petroulakis, E., Alain, T., Larsson, O., Mathonnet, G., Tettweiler, G., Hellen, C. U., Pestova, T. V., Svitkin, Y. V., Sonenberg, N. (2009). The helicase protein DHX29 promotes translation initiation, cell proliferation, and tumorigenesis. Proc. Natl. Acad. Sci. USA 106: 22217-22222 [Abstract] [Full Text]  
• Meric-Bernstam, F., Gonzalez-Angulo, A. M. (2009). Targeting the mTOR Signaling Network for Cancer Therapy. JCO 27: 2278-2287 [Abstract] [Full Text]  
• Muggia, F. M., Peters, G. J., Landolph, J. R. Jr. (2009). XIII International Charles Heidelberger Symposium and 50 Years of Fluoropyrimidines in Cancer Therapy Held on September 6 to 8, 2007 at New York University Cancer Institute, Smilow Conference Center. Molecular Cancer Therapeutics 8: 992-999 [Abstract] [Full Text]  
• LeBrasseur, N. (2008). An eIF for proliferation. JCB 181: 175-175 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents