| Autor: |
Nahum Sonenberg, Peng Wang, Zixian Li, Sunghoon Kim, Hao Huang, Jung-Hyun Choi, Haijin Xu, chutong yang, Abby Snape, Sara Bermudez, Marie-Noëlle Boivin, Nicolas Ferry, Rapita Sood, Vijendra Sharma, Joel Ryan, Morag Park, Jason Karamchandani, Bhushan Nagar |
| Rok vydání: |
2023 |
| DOI: |
10.21203/rs.3.rs-2847028/v1 |
| Popis: |
The mRNA 5’cap-binding eukaryotic translation initiation factor 4E (eIF4E) plays a major role in 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 and pro-inflammatory proteins. Work on eIF4E phosphatases has been paltry. Here, we show that PPM1G is the phosphatase that dephosphorylates eIF4E. We describe the binding motif in PPM1G that shares an eIF4E binding site with eIF4G and 4E-binding proteins (4E-BPs). We show that PPM1G is a nucleocytoplasmic shuttling protein that dephosphorylates eIF4E in the cytoplasm. We demonstrate that PPM1G inhibits cell proliferation and the phospho-eIF4E-dependent synthesis of several proteins involved in cell proliferation, survival, and inflammatory response. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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