PXD030415

PXD030415 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-15 04:30:31	ID requested
⏵ 1	2022-02-23 20:06:20	announced

Dataset with its publication pending

submitter keyword: ATG9A,TRAF6,Ubiquitin

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

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PRIDE project URI

• PRIDE
  1. PXD030415
     1. Label: PRIDE project
     2. Name: K48/K63-linked polyubiquitination of ATG9A at K581/K838 by TRAF6 E3 ligase