Eukaryotic initiation factor 4E (eIF4E): A recap of the cap-binding protein

J Cell Biochem. 2019 Sep;120(9):14201-14212. doi: 10.1002/jcb.28851. Epub 2019 May 9.

Abstract

Eukaryotic initiation factor 4E (eIF4E), a fundamental effector and rate limiting element of protein synthesis, binds the 7-methylguanosine cap at the 5' end of eukaryotic messenger RNA (mRNA) specifically as a constituent of eIF4F translation initiation complex thus facilitating the recruitment of mRNA to the ribosomes. This review focusses on the engagement of signals contributing to growth factor originated maxim and their role in the activation of eIF4E to achieve a collective influence on cellular growth, with a key focus on conjuring vital processes like protein synthesis. The review invites considerable interest in elevating the appeal of eIF4E beyond its role in regulating translation viz a viz cancer genesis, attributed to its phosphorylation state that improves the prospect for the growth of the cancerous cell. This review highlights the latest studies that have envisioned to target these pathways and ultimately the translational machinery for therapeutic intervention. The review also brings forward the prospect of eIF4E to act as a converging juncture for signaling pathways like mTOR/PI3K and Mnk/MAPK to promote tumorigenesis.

Keywords: Mnk; eIF4E; mTOR; translation; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Eukaryotic Initiation Factor-4E / genetics
  • Eukaryotic Initiation Factor-4E / metabolism*
  • Guanosine / analogs & derivatives*
  • Guanosine / metabolism
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Phosphorylation
  • Protein Biosynthesis*
  • RNA Cap-Binding Proteins / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism*
  • Ribosomes / genetics
  • Ribosomes / metabolism*
  • Signal Transduction

Substances

  • Eukaryotic Initiation Factor-4E
  • RNA Cap-Binding Proteins
  • RNA, Messenger
  • Guanosine
  • 7-methylguanosine