helicase protein DHX29 promotes translation initiation, cell proliferation, and tumorigenesis

Translational control plays an important role in cell growth and tumorigenesis. Cap-dependent translation initiation of mammalian mRNAs with structured 5'UTRs requires the DExH-box protein, DHX29, in vitro. Here we show that DHX29 is important for translation in vivo. Down-regulation of DHX29 l...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 52; pp. 22217 - 22222
Main Authors:	Parsyan, Armen, Shahbazian, David, Martineau, Yvan, Petroulakis, Emmanuel, Alain, Tommy, Larsson, Ola, Mathonnet, Geraldine, Tettweiler, Gritta, Hellen, Christopher U, Pestova, Tatyana V, Svitkin, Yuri V, Sonenberg, Nahum
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 29-12-2009 National Acad Sciences
Subjects:	5' Untranslated Regions Animals Biological Sciences Cancer Cell culture Cell growth Cell lines Cell Proliferation Down-Regulation Five prime untranslated regions HeLa Cells Humans Mammals Medicin och hälsovetenskap Messenger RNA Mice Mice, Nude Neoplasm Transplantation Neoplasms - enzymology Neoplasms - etiology Neoplasms - genetics Neoplasms - pathology Peptide Chain Initiation, Translational - physiology Peptide initiation factors Polyribosomes Proteins Ribosome Subunits, Small, Eukaryotic - metabolism Ribosomes RNA Helicases - antagonists & inhibitors RNA Helicases - genetics RNA Helicases - metabolism RNA Interference RNA, Messenger - genetics RNA, Messenger - metabolism RNA, Small Interfering - genetics Small interfering RNA Transplantation, Heterologous Tumors
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Summary:	Translational control plays an important role in cell growth and tumorigenesis. Cap-dependent translation initiation of mammalian mRNAs with structured 5'UTRs requires the DExH-box protein, DHX29, in vitro. Here we show that DHX29 is important for translation in vivo. Down-regulation of DHX29 leads to impaired translation, resulting in disassembly of polysomes and accumulation of mRNA-free 80S monomers. DHX29 depletion also impedes cancer cell growth in culture and in xenografts. Thus, DHX29 is a bona fide translation initiation factor that potentially can be exploited as a target to inhibit cancer cell growth.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 1A.P. and D.S. contributed equally to this work. 3Present address: Laboratory of Cytogenetics, Genetics Service, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Quebec, Canada H3T 1C5. Edited by Michael Karin, University of California San Diego School of Medicine, La Jolla, CA, and approved October 26, 2009 Author contributions: A.P., T.V.P., Y.V.S., and N.S. designed research; A.P., D.S., Y.M., E.P., and Y.V.S. performed research; A.P., D.S., Y.M., E.P., T.A., O.L., G.M., G.T., C.U.H., and T.V.P. contributed new reagents/analytic tools; A.P., D.S., Y.M., E.P., Y.V.S., and N.S. analyzed data; and A.P., C.U.H., T.V.P., Y.V.S., and N.S. wrote the paper. 2Present address: Department of Pharmacology, School of Medicine, Yale University, New Haven, CT 06511.
ISSN:	0027-8424 1091-6490 1091-6490
DOI:	10.1073/pnas.0909773106