PMID- 20086100 OWN - NLM STAT- MEDLINE DCOM- 20100409 LR - 20211020 IS - 1098-5549 (Electronic) IS - 0270-7306 (Print) IS - 0270-7306 (Linking) VI - 30 IP - 6 DP - 2010 Mar TI - Control of cell survival and proliferation by mammalian eukaryotic initiation factor 4B. PG - 1478-85 LID - 10.1128/MCB.01218-09 [doi] AB - 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. FAU - Shahbazian, David AU - Shahbazian D AD - Department of Biochemistry and Goodman Cancer Centre, McGill University, The Cancer Research Building, 1160 Pine Avenue West, Room 615, Montreal, Quebec H3A 1A3, Canada. FAU - Parsyan, Armen AU - Parsyan A FAU - Petroulakis, Emmanuel AU - Petroulakis E FAU - Topisirovic, Ivan AU - Topisirovic I FAU - Martineau, Yvan AU - Martineau Y FAU - Gibbs, Bernard F AU - Gibbs BF FAU - Svitkin, Yuri AU - Svitkin Y FAU - Sonenberg, Nahum AU - Sonenberg N LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100119 PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (5' Untranslated Regions) RN - 0 (Eukaryotic Initiation Factors) RN - 0 (RNA, Messenger) RN - 0 (eIF-4B) RN - EC 3.4.22.- (Caspases) RN - XT3Z54Z28A (Camptothecin) SB - IM MH - 5' Untranslated Regions MH - Apoptosis/drug effects MH - Camptothecin/pharmacology MH - Caspases/metabolism MH - Cell Proliferation/drug effects MH - Cell Survival/drug effects MH - Enzyme Activation/drug effects MH - Eukaryotic Initiation Factors/*metabolism MH - Gene Silencing/drug effects MH - HeLa Cells MH - Humans MH - Protein Biosynthesis/drug effects MH - RNA, Messenger/genetics/metabolism PMC - PMC2832492 EDAT- 2010/01/21 06:00 MHDA- 2010/04/10 06:00 PMCR- 2010/09/01 CRDT- 2010/01/21 06:00 PHST- 2010/01/21 06:00 [entrez] PHST- 2010/01/21 06:00 [pubmed] PHST- 2010/04/10 06:00 [medline] PHST- 2010/09/01 00:00 [pmc-release] AID - MCB.01218-09 [pii] AID - 1218-09 [pii] AID - 10.1128/MCB.01218-09 [doi] PST - ppublish SO - Mol Cell Biol. 2010 Mar;30(6):1478-85. doi: 10.1128/MCB.01218-09. Epub 2010 Jan 19.