The 14th D. Harold Copp Lecture

Translational control of cancer and brain diseases via the mRNA cap-binding protein, eIF4E

Dr. Nahum Sonenberg, M.D

Genentech, Inc., San Francisco, USA

Professor, FRS
Gilman Cheney Chair in Biochemistry
Goodman Cancer Research Center
McGill University

2002 Robert L. Noble Prize
2005 Killam Prize
2008 Gairdner International Award
2014 Wolf Prize

Dr. Sonenberg is the father of translational control that plays a critical role in essential cellular processes including cell growth, proliferation, development, and learning and memory. Under most circumstances, translational control is exerted at the initiation step in which the eukaryotic translation initiation factor 4E (eIF4E) interacts with the mRNA 5’cap structure to facilitate the recruitment of ribosomes and promote translation. Importantly, eIF4E preferentially stimulates the translation of a subset of mRNAs. The activity of eIF4E is regulated chiefly by two major signalling pathways: PI3K/Akt/mTOR and Ras/MAPK/Mnk. mTOR directly phosphorylates the 4E-BPs (eIF4E-binding proteins), which are inhibitors of eIF4E, to relieve translational suppression, while Mnk phosphorylates eIF4E to stimulate translation. Aberrations in these pathways result in dysregulated eIF4E activity, which engenders tumorigenesis and neurological disorders such as autism, Fragile X Syndrome and depression.