Eukaryotic translation initiation factor 3 (eIF3) subunit e is essential for embryonic development and cell proliferation

Mammalian eukaryotic translation initiation factor 3 (eIF3) is the largest complex of the translation initiation factors. The eIF3 complex is comprised of thirteen subunits, which are named eIF3a to eIF3 m in most multicellular organisms. The eIF3e gene locus is one of the most frequent integration...

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Published in:FEBS open bio 2018-08, Vol.8 (8), p.1188-1201
Main Authors: Sadato, Daichi, Ono, Tomio, Gotoh‐Saito, Saki, Kajiwara, Naoki, Nomura, Namiko, Ukaji, Masako, Yang, Liying, Sakimura, Kenji, Tajima, Youichi, Oboki, Keisuke, Shibasaki, Futoshi
Format: Article
Language:English
Subjects:
Cell growth
Cell proliferation
Cloning
Deoxyribonucleic acid
DNA
eIF3e
Embryo fibroblasts
Embryogenesis
embryonic development
eukaryotic translation initiation factor 3
Fibroblasts
Gene expression
gene‐targeted mice
haploinsufficiency
Hypoxia
Immunoglobulins
Initiation factors
Int6
Integration
Protein synthesis
Proteins
translation
Tumors
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Summary:Mammalian eukaryotic translation initiation factor 3 (eIF3) is the largest complex of the translation initiation factors. The eIF3 complex is comprised of thirteen subunits, which are named eIF3a to eIF3 m in most multicellular organisms. The eIF3e gene locus is one of the most frequent integration sites of mouse mammary tumor virus (MMTV), which induces mammary tumors in mice. MMTV‐integration events result in the expression of C‐terminal‐truncated eIF3e proteins, leading to mammary tumor formation. We have shown that tumor formation can be partly caused by activation of hypoxia‐inducible factor 2α. To investigate the function of eIF3e in mammals, we generated eIF3e‐deficient mice. These eIF3e−/− mice are embryonically lethal, while eIF3e+/− mice are much smaller than wild‐type mice. In addition, eIF3e+/− mouse embryonic fibroblasts (MEFs) contained reduced levels of eIF3a and eIF3c subunits and exhibited reduced cellular proliferation. These results suggest that eIF3e is essential for embryonic development in mice and plays a role in maintaining eIF3 integrity. eIF3e−/− mice are embryonically lethal, while eIF3e+/− mice are much smaller than wild‐type mice. In addition, eIF3e+/− mouse embryonic fibroblasts contained reduced levels of eIF3a and eIF3c subunits and exhibited reduced cellular proliferation. These results suggest that eIF3e is essential for embryonic development and for maintaining eIF3 integrity.
ISSN:2211-5463
2211-5463
DOI:10.1002/2211-5463.12482