Eukaryotic translation initiation factors as promising targets in cancer therapy
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(2020) 18:175
REVIEW
Open Access
Eukaryotic translation initiation factors as promising targets in cancer therapy Peiqi Hao1,2†, Jiaojiao Yu1†, Richard Ward3, Yin Liu2, Qiao Hao2, Su An2* and Tianrui Xu2*
Abstract The regulation of the translation of messenger RNA (mRNA) in eukaryotic cells is critical for gene expression, and occurs principally at the initiation phase which is mainly regulated by eukaryotic initiation factors (eIFs). eIFs are fundamental for the translation of mRNA and as such act as the primary targets of several signaling pathways to regulate gene expression. Mis-regulated mRNA expression is a common feature of tumorigenesis and the abnormal activity of eIF complexes triggered by upstream signaling pathways is detected in many tumors, leading to the selective translation of mRNA encoding proteins involved in tumorigenesis, metastasis, or resistance to anti-cancer drugs, and making eIFs a promising therapeutic target for various types of cancers. Here, we briefly outline our current understanding of the biology of eIFs, mainly focusing on the effects of several signaling pathways upon their functions and discuss their contributions to the initiation and progression of tumor growth. An overview of the progress in developing agents targeting the components of translation machinery for cancer treatment is also provided. Keywords: eIF, mRNA translation, Cancer, MAPK, PI3K/Akt, mTOR
Background The regulation of gene expression in eukaryotes can occur at different stages including gene transcription and mRNA translation. In comparison with transcriptional control, translational regulation of pre-existing mRNAs provides more direct, rapid and sensitive changes in intracellular levels of the encoded proteins and thus cellular adaptation during physiological and pathological conditions by rapidly reprogramming the proteome expression without the requirement for changes in RNA synthesis. Eukaryotic mRNA translation is a very complicated process that consists of four major phases:initiation, elongation, termination and ribosome recycling, while the regulation takes place mainly at the initiation stage which is the rate-limiting step of protein synthesis among the four steps of translation [1]. The major regulators in the initiation stage are the eukaryotic translation initiation factors (eIFs). In fact, * Correspondence: [email protected]; [email protected] † Peiqi Hao and Jiaojiao Yu contributed equally to this work. 2 Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China Full list of author information is available at the end of the article
eukaryotes utilize many more initiation factors than do prokaryotes, reflecting the greater biological complexity of eukaryotic translation. First, in eukaryotes, the 43S ribosomal pre-initiation complex (PIC) which is composed of the 40S ribosomal subunit, the eIF2-GTP-initiating methionyl tRNA (Met-tRNAi) ternary complex and many other eIFs including eIF1, eIF1A, eIF3 and eIF5, is recruited to the 5
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