PXD050616-1
PXD050616 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Interplay between beta-propeller subunits WDR26 and muskelin regulates the CTLH E3 ligase supramolecular complex |
| Description | The Pro/N-degron recognizing C-terminal to LisH (CTLH) complex is an E3 ligase of emerging interest in the developmental field and for targeted protein degradation (TPD) modalities. The human CTLH complex forms distinct supramolecular ring-shaped structures dependent on the multimerization of WDR26 or muskelin beta-propeller proteins. Here, we find that, in human cells, CTLH complex E3 ligase activity is dictated by a dynamic exchange between WDR26 and muskelin in tandem with muskelin autoregulation. Proteomic experiments revealed that complex-associated muskelin protein turnover is a major ubiquitin-mediated degradation event dependent on the CTLH complex in unstimulated HeLa cells. We observed that muskelin and WDR26 binding to the scaffold of the complex is interchangeable, indicative of the formation of separate WDR26 and muskelin complexes, which correlated with distinct proteomes in WDR26 and muskelin knockout cells. We found that mTOR inhibition-induced degradation of Pro/N-degron containing protein HMGCS1 is distinctly regulated by a muskelin-specific CTLH complex. Finally, we found that mTOR inhibition also activated muskelin degradation, likely as an autoregulatory feedback mechanism to regulate CTLH complex activity. Thus, rather than swapping substrate receptors, the CTLH E3 ligase complex controls substrate selectivity and its autoregulation through exchanging its beta-propeller oligomeric subunits WDR26 and muskelin. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-11-29 |
| AnnouncementXML | Submission_2024-11-29_17:42:28.025.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Matthew Maitland |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | ubiquitination signature dipeptidyl lysine |
| Instrument | Q Exactive Plus |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-03-14 08:09:11 | ID requested | |
| ⏵ 1 | 2024-11-29 17:42:28 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: CTLH, Ubiquitination, E3 ligase |
Contact List
| Caroline Schild-Poulter | |
|---|---|
| contact affiliation | Western University |
| contact email | cschild-poulter@robarts.ca |
| lab head | |
| Matthew Maitland | |
| contact affiliation | University of Toronto |
| contact email | m.maitland@utoronto.ca |
| 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/v07/MSV000094320/ |
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