8pj2

Structural highlights

Disease

EIF3D_HUMAN Defects in EIF3D are associated with some cancers, such as prostate, breast and colon cancers. Disease susceptibility may be associated with variants affecting the gene represented in this entry. Down-regulation inhibits proliferation of cancers (PubMed:25322666, PubMed:25370813, PubMed:25682860, PubMed:26008152, PubMed:26036682, PubMed:26617750, PubMed:27035563).^{[1] [2] [3] [4] [5] [6] [7]}

Function

EIF3D_HUMAN mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, a complex required for several steps in the initiation of protein synthesis of a specialized repertoire of mRNAs (PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:18599441, PubMed:25849773). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). In the eIF-3 complex, EIF3D specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs (PubMed:27462815).^{[8] [9] [10]} (Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426).^[11]

References

1. ↑ Li H, Zhou F, Wang H, Lin D, Chen G, Zuo X, Sun L, Zhang X, Yang S. Knockdown of EIF3D suppresses proliferation of human melanoma cells through G2/M phase arrest. Biotechnol Appl Biochem. 2015 Sep-Oct;62(5):615-20. PMID:25322666 doi:10.1002/bab.1305
2. ↑ Yu X, Zheng B, Chai R. Lentivirus-mediated knockdown of eukaryotic translation initiation factor 3 subunit D inhibits proliferation of HCT116 colon cancer cells. Biosci Rep. 2014 Dec 12;34(6):e00161. PMID:25370813 doi:10.1042/BSR20140078
3. ↑ Ren M, Zhou C, Liang H, Wang X, Xu L. RNAi-Mediated Silencing of EIF3D Alleviates Proliferation and Migration of Glioma U251 and U87MG Cells. Chem Biol Drug Des. 2015 Oct;86(4):715-22. PMID:25682860 doi:10.1111/cbdd.12542
4. ↑ Lin Z, Xiong L, Lin Q. Knockdown of eIF3d inhibits cell proliferation through G2/M phase arrest in non-small cell lung cancer. Med Oncol. 2015 Jul;32(7):183. PMID:26008152 doi:10.1007/s12032-015-0625-8
5. ↑ Gao Y, Teng J, Hong Y, Qu F, Ren J, Li L, Pan X, Chen L, Yin L, Xu D, Cui X. The oncogenic role of EIF3D is associated with increased cell cycle progression and motility in prostate cancer. Med Oncol. 2015 Jul;32(7):518. PMID:26036682 doi:10.1007/s12032-015-0518-x
6. ↑ Fan Y, Guo Y. Knockdown of eIF3D inhibits breast cancer cell proliferation and invasion through suppressing the Wnt/β-catenin signaling pathway. Int J Clin Exp Pathol. 2015 Sep 1;8(9):10420-7. eCollection 2015 PMID:26617750
7. ↑ Pan XW, Chen L, Hong Y, Xu DF, Liu X, Li L, Huang Y, Cui LM, Gan SS, Yang QW, Huang H, Qu FJ, Ye JQ, Wang LH, Cui XG. EIF3D silencing suppresses renal cell carcinoma tumorigenesis via inducing G2/M arrest through downregulation of Cyclin B1/CDK1 signaling. Int J Oncol. 2016 Jun;48(6):2580-90. PMID:27035563 doi:10.3892/ijo.2016.3459
8. ↑ Zhou M, Sandercock AM, Fraser CS, Ridlova G, Stephens E, Schenauer MR, Yokoi-Fong T, Barsky D, Leary JA, Hershey JW, Doudna JA, Robinson CV. Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3. Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18139-44. PMID:18599441 doi:10.1073/pnas.0801313105
9. ↑ Lee AS, Kranzusch PJ, Cate JH. eIF3 targets cell-proliferation messenger RNAs for translational activation or repression. Nature. 2015 Jun 4;522(7554):111-4. doi: 10.1038/nature14267. Epub 2015 Apr 6. PMID:25849773 doi:http://dx.doi.org/10.1038/nature14267
10. ↑ Lee AS, Kranzusch PJ, Doudna JA, Cate JH. eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation. Nature. 2016 Aug 4;536(7614):96-9. PMID:27462815 doi:http://dx.doi.org/10.1038/nature18954
11. ↑ Poyry TA, Kaminski A, Connell EJ, Fraser CS, Jackson RJ. The mechanism of an exceptional case of reinitiation after translation of a long ORF reveals why such events do not generally occur in mammalian mRNA translation. Genes Dev. 2007 Dec 1;21(23):3149-62. doi: 10.1101/gad.439507. PMID:18056426 doi:http://dx.doi.org/10.1101/gad.439507