| 11533134 | eIF3d is an mRNA cap-binding protein that is required for specialized translation initiation. | Lee AS, etal., Nature. 2016 Aug 4;536(7614):96-9. | Eukaryotic mRNAs contain a 5' cap structure that is crucial for recruitment of the translation machinery and initiation of protein synthesis. mRNA recognition is thought to require direct interactions between eukaryotic initiation factor 4E (eIF4E) and the mRNA cap. However, translation of numerous capped mRNAs remains robust during cellular stress, early development, and cell cycle progression despite inactivation of eIF4E. Here we describe a cap-dependent pathway of translation initiation in human cells that relies on a previously unknown cap-binding activity of eIF3d, a subunit of the 800-kilodalton eIF3 complex. A 1.4 A crystal structure of the eIF3d cap-binding domain reveals unexpected homology to endonucleases involved in RNA turnover, and allows modelling of cap recognition by eIF3d. eIF3d makes specific contacts with the cap, as exemplified by cap analogue competition, and these interactions are essential for assembly of translation initiation complexes on eIF3-specialized mRNAs such as the cell proliferation regulator c-Jun (also known as JUN). The c-Jun mRNA further encodes an inhibitory RNA element that blocks eIF4E recruitment, thus enforcing alternative cap recognition by eIF3d. Our results reveal a mechanism of cap-dependent translation that is independent of eIF4E, and illustrate how modular RNA elements work together to direct specialized forms of translation initiation. | 27462815 | 2016-09-01 |
| 11522087 | Knockdown of EIF3D suppresses proliferation of human melanoma cells through G2/M phase arrest. | Li H, etal., Biotechnol Appl Biochem. 2015 Sep-Oct;62(5):615-20. doi: 10.1002/bab.1305. Epub 2015 Jan 12. | Skin cancer is the most common malignancy with increasing incidence rates worldwide. The advanced form of skin cancer, melanoma, is resistant to conventional treatment methods, which motivated researchers to identify an alternative effective therapeutic approach. This study was designed to identify the effects of small interfering RNA (si-RNA) mediated silencing of eukaryotic translation initiation factor 3, subunit D (EIF3D) against melanoma cell survival. Briefly, a lentivirus-mediated RNA interference system was employed to knock down EIF3D expression in A375 and A431 melanoma cells. The cell proliferation was analyzed by methylthiazoletetrazolium (MTT) and colony formation assays. The cell cycle progression was investigated using flow cytometry. Results revealed that si-RNA-mediated knockdown of EIF3D significantly reduced the gene and protein expression levels of EIF3D in melanoma cells. Furthermore, knockdown of EIF3D led to a significant reduction in cell proliferation due to G2 /M phase cell cycle arrest. Apparently, the study demonstrated the critical involvement of EIF3D in the survival and progression of melanoma cells and depletion of EIF3D could be developed as a possible therapeutic option in the gene-targeted treatment of melanoma. | 25322666 | 2015-08-01 |
| 11538596 | Knockdown of eIF3D inhibits breast cancer cell proliferation and invasion through suppressing the Wnt/beta-catenin signaling pathway. | Fan Y and Guo Y, Int J Clin Exp Pathol. 2015 Sep 1;8(9):10420-7. eCollection 2015. | eIF3D (eukaryotic translation initiation factor 3 subunit D) is one member of the eIF3 family and plays a critical role in translation initiation. Previous studies showed that it was involved in the development and progression of several tumors. However, the role of eIF3D in breast cancer and the un derlying mechanism is still unclear. Therefore, this study set out to investigate the role of eIF3D in breast cancer. Our results demonstrated that eIF3D is up-regulated in breast cancer cells. Knockdown of eIF3D inhibited breast cancer cell proliferation and invasion. In addition, knockdown of eIF3D inhibited the expression of beta-catenin, cyclin D1 and c-Myc in breast cancer cells. Taken together, our findings show that siRNA-eIF3D inhibits breast cancer cell proliferation and invasion through suppressing the Wnt/beta-catenin signaling pathway. Therefore, eIF3D may be a good molecular target for the prevention and treatment of breast cancer. | 26617750 | 1000-10-01 |
| 11353996 | RNAi-Mediated Silencing of EIF3D Alleviates Proliferation and Migration of Glioma U251 and U87MG Cells. | Ren M, etal., Chem Biol Drug Des. 2015 Oct;86(4):715-22. doi: 10.1111/cbdd.12542. Epub 2015 Jul 28. | As the most common primary malignant brain tumors, gliomas cause more years of life lost than do any other tumors. Recently, abnormalities of the eukaryotic initiation factors (EIFs) have been reported in gliomas. Yet the role of EIF3D, which encodes a subunit o f EIF3 multiprotein complex, remains poorly understood. In this study, we found EIF3D expression was positively correlated with WHO grades of gliomas. Furthermore, we employ lentivirus-mediated RNA interference (RNAi) to examine the physiological role of EIF3D in glioma cells. Decreased EIF3D expression in U251 and U87MG glioma cells caused a delay in cell growth and a disruption in colony formation. In addition, EIF3D knockdown induced G0/G1 phase cell cycle arrest and apoptosis. Cells with suppressed expression of EIF3D had a lower capacity to migrate in the transwell assay. These results suggest that EIF3D plays an important role in glioma development and may serve as a potential therapeutic target for human glioma. | 25682860 | 2015-07-01 |
