The m Subunit of Murine Translation Initiation Factor elF3 Maintains the Integrity of the elF3 Complex and Is Required for Embryonic Development, Homeostasis, and Organ Size Control
文献类型:期刊论文
作者 | Zeng, LY; Wan, YH; Li, D; Wu, J; Shao, ML; Chen, J; Hui, LJ; Ji, HB; Zhu, XL |
刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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出版日期 | 2013 |
卷号 | 288期号:42页码:30087-30093 |
关键词 | Embryo Mouse Genetics Protein Complexes Protein Stability Translation Initiation Factors Eukaryotic Initiation Factor Knock-out Mice |
通讯作者 | Zhu, XL (reprint author), Inst Biochem & Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,xlzhu@sibcb.ac.cn |
英文摘要 | Background: eIF3m is a non-core subunit of eIF3. Results: eIF3m deficiency in mice results in animal death and instability of other eIF3 subunits; haploinsufficiency reduces organ size. Conclusion: eIF3m is critical for eIF3 structure and function. Significance: Understanding the mechanism of eIF3 complex formation and its role in embryonic development and homeostasis is crucial for determining the physiological function of this eukaryotic translation factor. Mammalian eIF3 is composed of 13 subunits and is the largest eukaryotic initiation factor. eIF3 plays a key role in protein biosynthesis. However, it is not fully understood how different subunits contribute to the structural integrity and function of the eIF3 complex. Whether eIF3 is essential for embryonic development and homeostasis is also not known. Here, we show that eIF3m null embryos are lethal at the peri-implantation stage. Compound heterozygotes (eIF3m(flox/-)) or FABP4-Cre-mediated conditional knock-out mice are lethal at mid-gestation stages. Although the heterozygotes are viable, they show markedly reduced organ size and diminished body weight. Acute ablation of eIF3m in adult mouse liver leads to rapidly decreased body weight and death within 2 weeks; these effects are correlated with a severe decline of protein biogenesis in the liver. Protein analyses reveal that eIF3m deficiency significantly impairs the integrity of the eIF3 complex due to down-regulation of multiple other subunits. Two of the subunits, eIF3f and eIF3h, are stabilized by eIF3m through subcomplex formation. Therefore, eIF3m is required for the structural integrity and translation initiation function of eIF3. Furthermore, not only is eIF3m an essential gene, but its expression level is also important for mouse embryonic development and the control of organ size. |
学科主题 | Biochemistry & Molecular Biology |
类目[WOS] | Biochemistry & Molecular Biology |
关键词[WOS] | NEURONAL MIGRATION DEFECTS ; FACTOR EIF3 ; PREINITIATION COMPLEX ; PROTEIN-SYNTHESIS ; IN-VIVO ; EXPRESSION ; CANCER ; REVEALS ; BINDING ; INHIBITION |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000329868100009 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/476] ![]() |
专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
推荐引用方式 GB/T 7714 | Zeng, LY,Wan, YH,Li, D,et al. The m Subunit of Murine Translation Initiation Factor elF3 Maintains the Integrity of the elF3 Complex and Is Required for Embryonic Development, Homeostasis, and Organ Size Control[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2013,288(42):30087-30093. |
APA | Zeng, LY.,Wan, YH.,Li, D.,Wu, J.,Shao, ML.,...&Zhu, XL.(2013).The m Subunit of Murine Translation Initiation Factor elF3 Maintains the Integrity of the elF3 Complex and Is Required for Embryonic Development, Homeostasis, and Organ Size Control.JOURNAL OF BIOLOGICAL CHEMISTRY,288(42),30087-30093. |
MLA | Zeng, LY,et al."The m Subunit of Murine Translation Initiation Factor elF3 Maintains the Integrity of the elF3 Complex and Is Required for Embryonic Development, Homeostasis, and Organ Size Control".JOURNAL OF BIOLOGICAL CHEMISTRY 288.42(2013):30087-30093. |
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