PPM1G dephosphorylates eIF4E in control of mRNA translation and cell proliferation

• DOI: 10.26508/lsa.202402755
• Publication Date: 2024-08-07T14:55:21Z
• Authors: Peng Wang; Zixian Li; Sung-Hoon Kim; Haijin Xu; Hao Huang; Chutong Yang; Abby Snape; Jung-Hyun Choi; Sara Bermudez; Marie-Noelle Boivin; Nicolas Ferry; Jason Karamchandani; Bhushan Nagar; Nahum Sonenberg
• Keywords: 0303 health sciences; Protein Phosphatase 2C; 03 medical and health sciences; Eukaryotic Initiation Factor-4E; HEK293 Cells; Protein Biosynthesis; Phosphoprotein Phosphatases; Humans; Animals; RNA, Messenger; Phosphorylation; Research Articles; Cell Proliferation; Protein Binding

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.