PMID:20018725

Citation	Parsyan, A, Shahbazian, D, Martineau, Y, Petroulakis, E, Alain, T, Larsson, O, Mathonnet, G, Tettweiler, G, Hellen, CU, Pestova, TV, Svitkin, YV and Sonenberg, N (2009) The helicase protein DHX29 promotes translation initiation, cell proliferation, and tumorigenesis. Proc. Natl. Acad. Sci. U.S.A. 106:22217-22
Abstract	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.
Links	PubMed PMC2799747 Online version:10.1073/pnas.0909773106
Keywords	5' Untranslated Regions; Animals; Cell Proliferation; Down-Regulation; HeLa Cells; Humans; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms/enzymology; Neoplasms/etiology; Neoplasms/genetics; Neoplasms/pathology; Peptide Chain Initiation, Translational/physiology; RNA Helicases/antagonists & inhibitors; RNA Helicases/genetics; RNA Helicases/metabolism; RNA Interference; RNA, Messenger/genetics; RNA, Messenger/metabolism; RNA, Small Interfering/genetics; Ribosome Subunits, Small, Eukaryotic/metabolism; Transplantation, Heterologous
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:DHX29		GO:0022627: cytosolic small ribosomal subunit	ECO:0000314:		C		Human DHX29. Figure 1: Immunofluorescence shows DHX29 was enriched in 40S fractions. A low level of DHX29 was associated with 60S and 80S ribosomes.	complete CACAO 12402
HUMAN:DHX29		GO:0042255: ribosome assembly	ECO:0000315:		P		Human DHX29. In cells with silenced DHX using shRNA, polysome profiles showed a reduction in polysomes with concomitant increases in 40S, 60S, and 80S ribosome fractions (Fig. 3B).	complete CACAO 12403
HUMAN:DHX29		GO:0008494: translation activator activity	ECO:0000315:		F		Human DHX29. In control cells, Cdc25C mRNA sedimented predominantly with heavy polysomes, whereas in DHX29-silenced cells, it was shifted to light polysomes, indicating decreased translation initiation of this mRNA (Fig. 4A). In agreement with these findings, Cdc25C protein levels decreased by more than 3-fold on DHX29 silencing (Fig. 4B).	complete CACAO 12404
HUMAN:DHX29		GO:0008284: positive regulation of cell proliferation	ECO:0000315:		P		Human DHX29. HeLa cell proliferation was inhibited by almost 3-fold in DHX29 siRNA-silenced cells (Fig. 5A). Cell proliferation also was significantly (3-fold) inhibited by shRNA-mediated silencing of DHX29 after 4 days, compared with a nontargeting shRNA control (Fig. 5B). These results demonstrate that DHX29 is associated for cell proliferation.	complete CACAO 12405

References

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