PPM1G dephosphorylates eIF4E in control of mRNA translation and cell proliferation

Life Sci Alliance. 2024 Aug 7;7(10):e202402755. doi: 10.26508/lsa.202402755. Print 2024 Oct.

Abstract

The mRNA 5'cap-binding eukaryotic translation initiation factor 4E (eIF4E) plays a critical role in the control of mRNA translation in health and disease. One mechanism of regulation of eIF4E activity is via phosphorylation of eIF4E by MNK kinases, which promotes the translation of a subset of mRNAs encoding pro-tumorigenic proteins. Work on eIF4E phosphatases has been paltry. Here, we show that PPM1G is the phosphatase that dephosphorylates eIF4E. We describe the eIF4E-binding motif in PPM1G that is similar to 4E-binding proteins (4E-BPs). We demonstrate that PPM1G inhibits cell proliferation by targeting phospho-eIF4E-dependent mRNA translation.

MeSH terms

  • Animals
  • Cell Proliferation* / genetics
  • Eukaryotic Initiation Factor-4E* / genetics
  • Eukaryotic Initiation Factor-4E* / metabolism
  • HEK293 Cells
  • Humans
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Biosynthesis*
  • Protein Phosphatase 2C* / genetics
  • Protein Phosphatase 2C* / metabolism
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism

Substances

  • Eukaryotic Initiation Factor-4E
  • Protein Phosphatase 2C
  • RNA, Messenger
  • Phosphoprotein Phosphatases
  • EIF4E protein, human