EIF4G1 and Associated Diseases
EIF4G1 (Eukaryotic translation initiation factor 4G1) is an essential component of the translation initiation process in eukaryotes, and its aberrant expression induces disruption of life activities and the development of a variety of diseases. Gene therapy, a measure to precisely intervene in key genes of diseases by means of exogenous gene manipulation, has become a new technology for studying diseases and treatments. As an advanced professional platform in the field of gene therapy, Creative Biolabs provides customized gene therapy research services and solutions based on EIF4G1 and its related diseases.
Overview of EIF4G1 Gene
The EIF4G1 gene, a genome encoded by 31 exons located on chromosome 3q27.1, is a component of the eukaryotic translation initiation complex and is widely and abundantly expressed in various tissues. The EIF4G1-encoded protein is a scaffold protein that connects ribosomes to mRNA during eukaryotic translation initiation and serves as a central protein for translation initiation, capable of interacting with numerous translation initiation factors. It is a central protein in translation initiation and can interact with numerous translation initiation factors, including PABP, eIF family proteins, and the 40S ribosome.
Since the cap-dependent translation of mRNA involves the recognition of cap structures, the deconvolution of ATP-dependent secondary structures, and the recruitment of mRNA by ribosomes, EIF4G1 is engaged in regulating the translation initiation of mRNAs encoding genes related to mitochondria, cell survival and growth in response to cellular stress responses such as heat stress, endoplasmic reticulum stress and hypoxic stress. In addition, EIF4G1 is essential for vital activity, is closely related to proliferation, energy metabolism and mitochondrial activity, and plays an important role in regulating the translation of factors involved in these processes.
Fig.1 Model depicting the interplay between eIF4E, eIF4G1, and eIF1 in scanning-dependent translation. (Haimov, 2018)
EIF4G1-associated Tumors and Cancers
As it plays an essential regulatory function on growth, development and lifespan, abnormal expression of EIF4G1 induces the development of numerous diseases. Researchers have observed abnormal increases in EIF4G1 expression levels in a variety of tumors and cancers, including patients with lung cancer, breast cancer, epithelial ovarian cancer, pharyngeal cancer and nasopharyngeal cancer.
EIF4G1 in nasopharyngeal carcinoma was positively correlated with tumor grade, clinical stage and lymph node metastasis, and negatively correlated with patient survival. By silencing EIF4G1 in non-small cell lung cancer (NSCLC), one study found that it was closely associated with proliferation, non-adherent-dependent growth, migration and invasion of lung squamous carcinoma cells, equivalent to tumor proteins in the development of NSCLC. Aberrant overexpression of EIF4G1 facilitated DNA damage repair, reduced cellular autophagy and apoptosis, and further deterioration processes in cancer cells.
In contrast, a significant reduction in tumors was detected in transplanted tumor-bearing mice silenced with EIF4G1, which was associated with a slowing of the cell invasion and basement membrane invasion processes involved in EIF4G1, and also involved its activation of the expression of the core tumor suppressor protein programmed death protein 4. In addition, EIF4G1 mutations induce the development of Parkinson's disease, which is attributed to the impairment of the body's rapid dynamic response to emergencies caused by the mutation. In summary, multiple disease model studies have confirmed that EIF4G1 can be used as a potential therapeutic molecular target and prognostic indicator, providing current ideas for diagnosis, treatment and prognostic monitoring of the disease.
Fig.2 Model for EIF4G1 network in cancers. (Jaiswal, 2019)
Activation and expression of EIF4G1 is involved in cell survival, proliferation, cloning, migration, and ribosomal mRNA loading, and has an important role in the development and progression of several types of cancer. Targeted downregulation of EIF4G1 is a novel target for silencing tumor protein function based on gene therapy strategies. Creative Biolabs has established a well-established genetic engineering system including gene correction and replacement, gene enhancement and inactivation that can help you conduct research on EIF4G1-related diseases in a variety of target cells. Please contact us to discuss your projects.
References
- Haimov, O.; et al. Dynamic interaction of EIF4G1 with eIF4E and eIF1 underlies scanning-dependent and -independent translation. Mol Cell Biol. 2018, 38(18): e00139-18.
- Jaiswal, P.K.; et al. EIF4G1: a target for cancer therapeutic intervention? Cancer Cell Int. 2019, 19: 224.
