Control of cell survival and proliferation by mammalian eukaryotic initiation factor 4B.
Translation initiation plays an important role in cell growth, proliferation, and survival. The translation initiation factor eIF4B (eukaryotic initiation factor 4B) stimulates the RNA helicase activity of eIF4A in unwinding secondary structures in the 5' untranslated region (5'UTR) of the mRNA in vitro. Here, we studied the effects of eIF4B depletion in cells using RNA interference (RNAi). In agreement with the role of eIF4B in translation initiation, its depletion resulted in inhibition of this step. Selective reduction of translation was observed for mRNAs harboring strong to moderate secondary structures in their 5'UTRs. These mRNAs encode proteins, which function in cell proliferation (Cdc25C, c-myc, and ODC [ornithine decarboxylase]) and survival (Bcl-2 and XIAP [X-linked inhibitor of apoptosis]). Furthermore, eIF4B silencing led to decreased proliferation rates, promoted caspase-dependent apoptosis, and further sensitized cells to camptothecin-induced cell death. These results demonstrate that eIF4B is required for cell proliferation and survival by regulating the translation of proliferative and prosurvival mRNAs.
Shahbazian
David
D
Department of Biochemistry and Goodman Cancer Centre, McGill University, The Cancer Research Building, 1160 Pine Avenue West, Room 615, Montreal, Quebec H3A 1A3, Canada.
Parsyan
Armen
A
Petroulakis
Emmanuel
E
Topisirovic
Ivan
I
Martineau
Yvan
Y
Gibbs
Bernard F
BF
Svitkin
Yuri
Y
Sonenberg
Nahum
N
D020121:5' Untranslated Regions; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D039642:Eukaryotic Initiation Factors / Q000378:metabolism*; D020868:Gene Silencing / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D020121:5' Untranslated Regions; D039642:Eukaryotic Initiation Factors; D012333:RNA, Messenger; C031799:eIF-4B; D020169:Caspases; D002166:Camptothecin