PXD006288
PXD006288 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | SENP8 limits aberrant neddylation of NEDD8 pathway components to promote cullin- 1 RING ubiquitin ligase function |
| Description | NEDD8 is a ubiquitin-like modifier most well-studied for its role in activating the largest family of ubiquitin E3 ligases, the cullin-RING ligases (CRLs). While many non-cullin neddylation substrates have been proposed over the years, validation of true NEDD8 targets has been challenging, as overexpression of exogenous NEDD8 can trigger NEDD8 conjugation through the ubiquitylation machinery. Here, we developed a deconjugation-resistant form of NEDD8 to stabilize the neddylated form of cullins and other non-cullin substrates. Using this strategy, we identified Ubc12, a NEDD8-specific E2 conjugating enzyme, as a substrate for auto-neddylation both in vitro and in cells. Furthermore, we identified SENP8/DEN1 as the protease that counteracts Ubc12 auto-neddylation, and observed aberrant neddylation of Ubc12 and other NEDD8 conjugation pathway components in engineered SENP8-deficient cells. Importantly, loss of SENP8 function contributes to reduced CRL activity, accumulation of CRL substrates, and defective cell cycle progression. Thus, our study highlights the importance of SENP8 in maintaining proper neddylation levels and CRL-dependent proteostasis, implicating this protease as a potential therapeutic target for inhibiting CRL activity. |
| HostingRepository | MassIVE |
| AnnounceDate | 2017-04-13 |
| AnnouncementXML | Submission_2017-04-13_06:19:17.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Jessica Chapman |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | ubiquitination signature dipeptidyl lysine; unknown modification: neddylation |
| Instrument | Q Exactive |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2017-04-13 05:37:03 | ID requested | |
| ⏵ 1 | 2017-04-13 06:19:17 | announced |
Publication List
| Dataset with its publication pending |
Keyword List
| submitter keyword: FLAG-NEDD8, immunoprecipitation, SILAC |
Contact List
| Beatrix Ueberheide | |
|---|---|
| contact affiliation | NYU School of Medicine |
| contact email | beatrix.ueberheide@nyumc.org |
| lab head | |
| Jessica Chapman | |
| contact affiliation | NYU School of Medicine |
| contact email | jessica.chapman@nyumc.org |
| 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/MSV000080917 |
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