Abstract: Series 106, Lecture 5
The Harvey Lectures Series 106 (2010—2011)
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Lecture #5: Thursday, March 17, 2011 — Time and Location
Translational Control of Cancer
Nahum Sonenberg, PhD
James McGill Professor
Department of Biochemistry
Goodman Cancer Research Centre
McGill University
Montreal, Quebec, Canada
Control of mRNA translation plays an important role in the regulation of cell growth and proliferation. A number of translation factors are either overexpressed or their activity is dysregulated in human tumors. In addition, forced overexpression of several translation factors in cells and mice engenders malignant transformation. The PI3K/Akt/mTOR signaling pathway, which is frequently deregulated in cancer, is a major pathway impacting on the activity of translation factors. Key translation initiation factors, which are controlled by the PI3K/Akt/mTOR pathway, and are implicated in cancer, include the mRNA 5’-cap binding protein, eIF4E and its partners eIF4A and eIF4G, which together form the cap-binding protein complex, termed eIF4F. The RAS/RAF/MEK/ERK (MAPK) pathway, which is also deregulated in cancer, promotes the phosphorylation of eIF4E on Ser209 that is required for efficient transformation by eIF4E. We recently generated eIF4E ‘knock-in’ mice in which Ser209 was mutated to alanine. These mice were resistant to prostate cancer induced by PTEN deletion. Components of eIF4F have been recently targeted for cancer therapy with either small molecules or anti-sense approaches. These approaches have potential for developing new anti-cancer drugs.