PXD045603
PXD045603 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | STING induces LUBAC synthesis of linear ubiquitin chains to activate NFkB |
| Description | STING activation by cyclic dinucleotides in mammals induces Type I Interferon- and NFkB-related gene expression, and the lipidation of LC3B at Golgi membranes. While the mechanisms of the Interferon-related responses are well understood, the mechanism of NFkB activation mediated by STING activation, and how the multi-functional responses downstream of STING signaling are related remain unknown. We report that STING activation induces K63 and linear ubiquitin chain formation, and ubiquitin co-localizes with STING and LC3B at Golgi-derived vesicles. Loss of the LUBAC E3 ubiquitin ligase subunit, HOIP, prevents formation of the linear, but not K63-linked, ubiquitin chains. The ubiquitin and LC3B binding proteins, Optineurin and TNIP1, are co-localized with STING activation-induced, perinuclear LC3B foci via their UBAN domains, however loss of HOIP does not influence this localization, indicating they may bind the K63-linked ubiquitin chains. HOIP-mediated linear ubiquitin chains are well established to mediate NFkB downstream of TNFa and IL1beta receptor stimulation. Loss of HOIP in monocytic THP-1 cells inhibits STING-induced NFkB activation and NFkB-related gene transcription, as well as Interferon-related transcription. Further, the recently reported proton channel activity of STING that blocks LC3B lipidation at Golgi membranes is also important for both K63 and Linear ubiquitin chain formation, and NFkB signaling. Thus, STING induces HOIP and linear ubiquitin chain formation to activate NFkB. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-10-18 |
| AnnouncementXML | Submission_2024-10-18_07:03:02.427.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Yan Wang |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | GG |
| Instrument | Orbitrap Fusion Lumos |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2023-09-22 12:54:39 | ID requested | |
| ⏵ 1 | 2024-10-18 07:03:02 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: STING activation, linear, K48, K63 polyubiqitin chains, NFkB signaling |
Contact List
| Yan Wang | |
|---|---|
| contact affiliation | NIH/NIDCR |
| contact email | wangyan2@nih.gov |
| lab head | |
| Yan Wang | |
| contact affiliation | NIH |
| contact email | yan.wang2@nih.gov |
| 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/v06/MSV000092940/ |
to receive all new ProteomeXchange dataset release announcements!
