1. eIF4E Phosphorylation in Prostate Cancer
- Author
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Leandro S. D'Abronzo and Paramita M. Ghosh
- Subjects
Male ,0301 basic medicine ,Cancer Research ,PRAS40, 40 kDa pro-rich Akt substrate ,4EBP1, eukaryotic translation initiation factor 4E binding protein 1 ,eIF, eukaryotic initiation factor ,chemistry.chemical_compound ,ITAFs, IRES trans-acting factors ,Eukaryotic initiation factor ,Phosphorylation ,CYP17A, cytochrome P450 17A1 ,MTC, medullary thyroid carcinoma ,biology ,EIF4G ,RICTOR, rapamycin insensitive companion of mTOR ,EIF4E ,PROTOR, protein observer of RICTOR ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,eIF4E, eukaryotic translation initiation factor 4E ,Rheb, Ras homolog enriched in brain ,FKBP12, FK506 binding protein 12 ,3. Good health ,IRES, internal ribosome entry site ,MTA1, metastasis associated protein ,HSP, heat shock protein ,Mitogen-Activated Protein Kinases ,PI3K, phosphoinositide 3-kinase ,Signal Transduction ,PIN, prostate intraepithelial neoplasia ,PCa, prostate cancer ,mTOR, mammalian target of rapamycin ,SRPK, Ser/Arg (SR)-rich protein kinase ,EMT, epithelial mesenchymal transition ,lcsh:RC254-282 ,03 medical and health sciences ,Review article ,mSIN1, mammalian stress-activated map kinase-interacting protein 1 ,MEK, mitogen-activated protein kinase kinase ,Humans ,BPH, benign prostate hyperplasia ,RNA, Messenger ,ADT, androgen deprivation therapy ,Mechanistic target of rapamycin ,Protein kinase B ,PI3K/AKT/mTOR pathway ,CRPC, castration resistant prostate cancer ,Prostatic Neoplasms ,RAPTOR, regulatory associated protein or mTOR ,Mnk, mitogen activated protein kinase interacting protein kinase ,PTEN, phosphatase and tensin homolog ,LARP1 ,EGFR, epidermal growth factor receptor ,TOP, 5′-Terminal OligoPyrimidine ,Internal ribosome entry site ,Eukaryotic Initiation Factor-4E ,030104 developmental biology ,chemistry ,biology.protein ,Cancer research ,MAPK, mitogen-activated protein kinase ,LARP1, La-related protein 1 - Abstract
Prostate cancer (PCa) progression involves a shift from endocrine to paracrine and eventually autocrine control resulting from alterations in molecular mechanisms in the cells. Deregulation of RNA translation is crucial for tumor cells to grow and proliferate; therefore, overactivation of the translation machinery is often observed in cancer. The two most important signal transduction pathways regulating PCa progression are PI3K/Akt/mTOR and Ras/MAPK. These two pathways converge on the eukaryotic translation initiation factor 4E (eIF4E) which binds to the protein scaffold eIF4G upon mechanistic target of rapamycin (mTOR) activation and is phosphorylated by the mitogen-activated protein kinase (MAPK) interacting protein kinases (Mnk1/2). This review describes the role of eIF4E in mRNA translation initiation mediated by its binding to the methylated 5′ terminal structure (m7G-cap) of many mRNAs, and the ability of many tumor cells to bypass this mechanism. Hormonal therapy and chemotherapy are two of the most prevalent therapies used in patients with advanced PCa, and studies have implicated a role for eIF4E phosphorylation in promoting resistance to both these therapies. It appears that eIF4E phosphorylation enhances the rate of translation of oncogene mRNAs to increase tumorigenicity.
- Published
- 2018
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