PXD042771
PXD042771 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Deoxyhypusine synthase (DHPS) mutations alter the post-translational modification of eukaryotic initiation factor 5A (eIF5A) resulting in impaired human and mouse neural homeostasis |
| Description | DHPS deficiency is a rare genetic disease caused by biallelic hypomorphic variants in the Deoxyhypusine synthase (DHPS) gene. The DHPS enzyme functions in mRNA translation by catalyzing the post-translational modification, and therefore activation, of the eukaryotic initiation factor 5A (eIF5A). The observed clinical outcomes associated with human mutations in DHPS include developmental delay, intellectual disability, and seizures. Therefore, to increase our understanding of this rare disease, it is critical to determine the mechanisms by which mutations in DHPS alter neurodevelopment. In this study, we have generated patient-derived lymphoblast cell lines and demonstrated that human DHPS variants alter DHPS protein abundance and impair enzyme function. Moreover, we observe a shift in the abundance of the post-translationally modified forms of eIF5A, specifically, an increase in the nuclear localized acetylated form (eIF5AAcK47) and concomitant decrease in the cytoplasmic localized hypusinated form (eIF5AHYP). Generation and characterization of a mouse model with a genetic deletion of Dhps in the brain at birth shows that loss of hypusine biosynthesis impacts neuronal function due to impaired eIF5AHYP-dependent mRNA translation; this translation defect results in altered expression of proteins required for proper neuronal development and function. This study reveals new insight into the biological consequences and molecular impact of human DHPS deficiency and provides valuable information towards the goal of developing treatment strategies for this rare disease. |
| HostingRepository | MassIVE |
| AnnounceDate | 2023-06-06 |
| AnnouncementXML | Submission_2023-06-06_14:28:57.257.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | Emma Doud |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | TMT6plex; Oxidation |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2023-06-06 12:12:55 | ID requested | |
| ⏵ 1 | 2023-06-06 14:28:57 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: DHPS deficiency, DHPS, eIF5A, hypusination, hypusine, mRNA translation, neurodevelopment, rare disease |
Contact List
| Teresa Mastracci | |
|---|---|
| contact affiliation | Indiana University-Purdue University-Indianapolis |
| contact email | tmastrac@iu.edu |
| lab head | |
| Amber L. Mosley | |
| contact affiliation | Indiana University School of Medicine |
| contact email | almosley@iu.edu |
| lab head | |
| Emma Doud | |
| contact affiliation | IUSM |
| contact email | edoud@iu.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000092112/ |
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