PXD030415 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | K48/K63-linked polyubiquitination of ATG9A at K581/K838 by TRAF6 E3 ligase |
Description | Excessive generation and accumulation of highly reactive oxidizing molecules causes oxidative stress and oxidative damage to cellular components. Accumulating evidence indicates that autophagy diminishes oxidative damage in cells and maintains redox homeostasis by degrading and recycling intracellular damaged components. However, the molecular mechanisms underlying the activation of oxidative stress-mediated autophagic response remain elusive. Here we show that ubiquitin E3 ligase TNF receptor-associated factor 6 (TRAF6) and the deubiquitinase A20 coordinate to regulate ATG9A ubiquitination and autophagy activation in cells responding to oxidative stress. The reactive oxygen species (ROS)-dependent TRAF6-mediated non-proteolytic, K48/63-linked ubiquitination of ATG9A enhances its association with Beclin 1 and the assembly of class III phosphatidylinositol-3-kinase (PI3KC3/VPS34) UVRAG complex, thereby stimulating autophagy. Notably, depletion of ATG9A or expression of the ATG9A ubiquitination mutants markedly decreases ROS-induced VPS34 activation and autophagy. We further find that lipopolysaccharide (LPS)-induced ROS production also stimulates TRAF6-mediated ATG9A ubiquitination and enhances the assembly of the UVRAG-containing VPS34 complex in an ATG9A-dependent manner. Ablation of ATG9A causes aberrant TLR4 endosomal trafficking and decreased phosphorylation of IRF-3 in LPS-stimulated macrophages. Our findings provide important insight into how K48/K63-linked ubiquitination of ATG9A contributes to the regulation of oxidative stress-induced autophagy. |
HostingRepository | PRIDE |
AnnounceDate | 2022-02-24 |
AnnouncementXML | Submission_2022-02-23_20:06:19.936.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | YI-TING WANG |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | ubiquitinylated lysine |
Instrument | Orbitrap Fusion |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2021-12-15 04:30:31 | ID requested | |
⏵ 1 | 2022-02-23 20:06:20 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: ATG9A,TRAF6,Ubiquitin |
Contact List
Guang-Chao Chen |
contact affiliation | Academia Sinica,Institute of Biological Chemistry |
contact email | gcchen@gate.sinica.edu.tw |
lab head | |
YI-TING WANG |
contact affiliation | Institute of Biological Chemistry, Academia Sinica |
contact email | pink791122@hotmail.com |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD030415
- Label: PRIDE project
- Name: K48/K63-linked polyubiquitination of ATG9A at K581/K838 by TRAF6 E3 ligase