Summary of Study ST002119
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
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002119 |
| Study Title | Metabolomics analysis of zebrafish response to CID661578 treatment |
| Study Summary | zebrafish larvae were treated with DMSO or CID661578 for 24 hours prior to global metabolomics analysis (n=6). Metabolites were extracted from pools of 10 zebrafish larvae at 5 dpf using a 80% methanol-based extraction method. Samples were dried in speed vac and stored in -80C freezer until ready for LC-MS analysis. |
| Institute | North Carolina State University |
| Last Name | Liu |
| First Name | Xiaojing |
| Address | Polk Hall, RM 128 |
| xliu68@ncsu.edu | |
| Phone | 9195154387 |
| Submit Date | 2022-03-30 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2022-04-14 |
| Release Version | 1 |
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Project:
| 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 |
