Summary of project PR001344
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001344. The data can be accessed directly via it's Project DOI: 10.21228/M80D9F This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001344 |
| Project DOI: | doi: 10.21228/M80D9F |
| Project Title: | MNK2 deficiency potentiates beta-cell regeneration via hypertranslation |
| Project Summary: | Regenerating pancreatic beta-cells is a potential curative approach for diabetes. We previously identified the small molecule CID661578 as a potent inducer of beta-cell regeneration but its target and mechanism of action have remained unknown. We now screened 257 million yeast clones and determined that CID661578 targets MAP kinase-interacting serine/threonine kinase 2 (MNK2), an interaction we genetically validated in vivo. CID661578 increased beta-cell neogenesis from ductal cells in zebrafish, neonatal pig islet aggregates and human pancreatic ductal organoids. Mechanistically, we found that CID661578 boosts protein synthesis and regeneration by blocking MNK2 from binding eIF4G in the translation initiation complex at the mRNA cap. Unexpectedly, this blocking activity augmented eIF4E-phosphorylation depending on MNK1 and bolstered the interaction between eIF4E and eIF4G, which is necessary for both hypertranslation and beta-cell regeneration. Taken together, our findings demonstrate a targetable role of MNK2-controlled translation in beta-cell regeneration, a role that warrants further investigation in diabetes. |
| Institute: | North Carolina State University |
| Last Name: | Liu |
| First Name: | Xiaojing |
| Address: | Polk Hall, RM 128 |
| Email: | xliu68@ncsu.edu |
| Phone: | 9195154387 |
Summary of all studies in project PR001344
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002119 | Metabolomics analysis of zebrafish response to CID661578 treatment | Danio rerio | North Carolina State University | MS | 2022-04-14 | 1 | 36 | Uploaded data (2.5G)* |
