解旋酶蛋白 DHX29 可促进翻译起始、细胞增殖和肿瘤发生。
The helicase protein DHX29 promotes translation initiation, cell proliferation, and tumorigenesis.
机构信息
Department of Biochemistry, Faculty of Medicine and Goodman Cancer Center, McGill University, Montreal, Quebec, Canada.
出版信息
Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22217-22. doi: 10.1073/pnas.0909773106. Epub 2009 Dec 11.
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.
摘要
翻译控制在细胞生长和肿瘤发生中起着重要作用。体外实验表明，具有结构 5'UTR 的哺乳动物 mRNAs 的帽依赖性翻译起始需要 DExH 盒蛋白 DHX29。在这里，我们表明 DHX29 对体内翻译很重要。DHX29 的下调导致翻译受损，导致多核糖体解体和无 mRNA 的 80S 单体积累。DHX29 耗尽也会阻碍培养和异种移植中的癌细胞生长。因此，DHX29 是一种真正的翻译起始因子，可能可被用作抑制癌细胞生长的靶标。
相似文献
1
The helicase protein DHX29 promotes translation initiation, cell proliferation, and tumorigenesis.
Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22217-22. doi: 10.1073/pnas.0909773106. Epub 2009 Dec 11.
2
Translation initiation on mammalian mRNAs with structured 5'UTRs requires DExH-box protein DHX29.
Cell. 2008 Dec 26;135(7):1237-50. doi: 10.1016/j.cell.2008.10.037.
3
DHX29 and eIF3 cooperate in ribosomal scanning on structured mRNAs during translation initiation.
RNA. 2016 Dec;22(12):1859-1870. doi: 10.1261/rna.057851.116. Epub 2016 Oct 12.
4
Functional role and ribosomal position of the unique N-terminal region of DHX29, a factor required for initiation on structured mammalian mRNAs.
Nucleic Acids Res. 2021 Dec 16;49(22):12955-12969. doi: 10.1093/nar/gkab1192.
5
The DHX33 RNA Helicase Promotes mRNA Translation Initiation.
Mol Cell Biol. 2015 Sep 1;35(17):2918-31. doi: 10.1128/MCB.00315-15. Epub 2015 Jun 22.
6
Roles of helicases in translation initiation: a mechanistic view.
Biochim Biophys Acta. 2013 Aug;1829(8):799-809. doi: 10.1016/j.bbagrm.2013.01.005. Epub 2013 Jan 19.
7
Selective 40S Footprinting Reveals Cap-Tethered Ribosome Scanning in Human Cells.
Mol Cell. 2020 Aug 20;79(4):561-574.e5. doi: 10.1016/j.molcel.2020.06.005. Epub 2020 Jun 25.
8
Targeting the eIF4A RNA helicase as an anti-neoplastic approach.
Biochim Biophys Acta. 2015 Jul;1849(7):781-91. doi: 10.1016/j.bbagrm.2014.09.006. Epub 2014 Sep 16.
9
Structure of the mammalian ribosomal 43S preinitiation complex bound to the scanning factor DHX29.
Cell. 2013 May 23;153(5):1108-19. doi: 10.1016/j.cell.2013.04.036.
10
Found in translation: another RNA helicase function.
Mol Cell. 2008 Dec 26;32(6):755-6. doi: 10.1016/j.molcel.2008.12.008.
引用本文的文献
1
The translation initiation factor DHX29 appears to pull on mRNA in a direction opposite to scanning.
bioRxiv. 2025 Jul 14:2025.07.13.664561. doi: 10.1101/2025.07.13.664561.
2
The evolution and genetic basis of a functionally critical skull bone, the parasphenoid, among Lake Malawi cichlids.
Evol J Linn Soc. 2024 Dec 5;3(1):kzae039. doi: 10.1093/evolinnean/kzae039. eCollection 2024.
3
Specific human gene expression in response to infection is an effective marker for diagnosis of latent and active tuberculosis.
Sci Rep. 2024 Nov 6;14(1):26884. doi: 10.1038/s41598-024-77164-5.
4
Genome-wide quantification of RNA flow across subcellular compartments reveals determinants of the mammalian transcript life cycle.
Mol Cell. 2024 Jul 25;84(14):2765-2784.e16. doi: 10.1016/j.molcel.2024.06.008. Epub 2024 Jul 3.
5
YLR419W is the homolog of the mammalian translation initiation factor .
MicroPubl Biol. 2024 Feb 22;2024. doi: 10.17912/micropub.biology.001112. eCollection 2024.
6
High-Throughput Antigen Microarray Identifies Longitudinal Prognostic Autoantibody for Chemoimmunotherapy in Advanced Non-Small Cell Lung Cancer.
Mol Cell Proteomics. 2024 May;23(5):100749. doi: 10.1016/j.mcpro.2024.100749. Epub 2024 Mar 20.
7
Structural insights into the N-terminal APHB domain of HrpA: mediating canonical and i-motif recognition.
Nucleic Acids Res. 2024 Apr 12;52(6):3406-3418. doi: 10.1093/nar/gkae138.
8
DHX37 Is a Promising Prognostic Biomarker and a Therapeutic Target for Immunotherapy and Chemotherapy in HCC.
Cancers (Basel). 2023 Oct 31;15(21):5228. doi: 10.3390/cancers15215228.
9
Functional role and ribosomal position of the unique N-terminal region of DHX29, a factor required for initiation on structured mammalian mRNAs.
Nucleic Acids Res. 2021 Dec 16;49(22):12955-12969. doi: 10.1093/nar/gkab1192.
10
Effect of p53 and its N-terminally truncated isoform, Δ40p53, on breast cancer migration and invasion.
Mol Oncol. 2022 Jan;16(2):447-465. doi: 10.1002/1878-0261.13118. Epub 2021 Nov 23.
本文引用的文献
1
Essential role for eIF4GI overexpression in the pathogenesis of inflammatory breast cancer.
Nat Cell Biol. 2009 Jul;11(7):903-8. doi: 10.1038/ncb1900. Epub 2009 Jun 14.
2
Characterization of the HDAC1 complex that regulates the sensitivity of cancer cells to oxidative stress.
Cancer Res. 2009 Apr 15;69(8):3597-604. doi: 10.1158/0008-5472.CAN-08-4368. Epub 2009 Apr 7.
3
Regulation of translation initiation in eukaryotes: mechanisms and biological targets.
Cell. 2009 Feb 20;136(4):731-45. doi: 10.1016/j.cell.2009.01.042.
4
Translation initiation on mammalian mRNAs with structured 5'UTRs requires DExH-box protein DHX29.
Cell. 2008 Dec 26;135(7):1237-50. doi: 10.1016/j.cell.2008.10.037.
5
Inactivation of the CYLD deubiquitinase by HPV E6 mediates hypoxia-induced NF-kappaB activation.
Cancer Cell. 2008 Nov 4;14(5):394-407. doi: 10.1016/j.ccr.2008.10.007.
6
Reduced eukaryotic initiation factor 2Bepsilon-subunit expression suppresses the transformed phenotype of cells overexpressing the protein.
Cancer Res. 2008 Nov 1;68(21):8752-60. doi: 10.1158/0008-5472.CAN-08-1042.
7
Poly(A)-binding protein-interacting protein 1 binds to eukaryotic translation initiation factor 3 to stimulate translation.
Mol Cell Biol. 2008 Nov;28(21):6658-67. doi: 10.1128/MCB.00738-08. Epub 2008 Aug 25.
8
UNAFold: software for nucleic acid folding and hybridization.
Methods Mol Biol. 2008;453:3-31. doi: 10.1007/978-1-60327-429-6_1.
9
The DEAD-box RNA helicase DDX3 associates with export messenger ribonucleoproteins as well as tip-associated protein and participates in translational control.
Mol Biol Cell. 2008 Sep;19(9):3847-58. doi: 10.1091/mbc.e07-12-1264. Epub 2008 Jul 2.
10
Control of eIF4E cellular localization by eIF4E-binding proteins, 4E-BPs.
RNA. 2008 Jul;14(7):1318-27. doi: 10.1261/rna.950608. Epub 2008 May 30.
Zotero 插件