PXD059866

PXD059866 is an original dataset announced via ProteomeXchange.

Title	Aspirin inhibits proteasomal degradation and promotes α-synuclein aggregate clearance through K63 ubiquitination
Description	Aspirin is a potent lysine acetylation inducer, but its impact on lysine ubiquitination and ubiquitination-directed protein degradation is unclear. Herein, we develop the reversed-pulsed-SILAC strategy to systematically profile protein degradome in response to aspirin. By integrating degradome, acetylome, and ubiquitinome analyses, we show that aspirin impairs proteasome activity to inhibit proteasomal degradation, rather than directly suppressing lysine ubiquitination. Interestingly, aspirin increases lysosomal degradation-implicated K63-linked ubiquitination. Accordingly, using the major pathological protein of Parkinson's disease (PD), α-synuclein (α-syn), as an example of protein aggregates, we find that aspirin is able to reduce α-syn in cultured cells, neurons, and PD model mice with a rescued locomotor ability. We further reveal that the -syn aggregate clearance induced by aspirin is K63-ubiquitination dependent in both cells and PD mice. These findings suggest two complementary mechanisms by which aspirin regulates the degradation of soluble and insoluble proteins, providing new insights into its diverse pharmacological effects that can aid in future drug development efforts.
HostingRepository	iProX
AnnounceDate	2025-01-16
AnnouncementXML	Submission_2025-01-16_00:15:13.520.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jing Gao
SpeciesList	scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationList	acetylated residue; ubiquitination signature dipeptidyl lysine
Instrument	Orbitrap Fusion; Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-16 00:13:44	ID requested
⏵ 1	2025-01-16 00:15:13	announced

Dataset with its publication pending

submitter keyword: Aspirin, Acetylation, Protein degradation, Proteasome, K63 ubiquitination, a-synuclein

Yaoyang Zhang
contact affiliation	Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry
contact email	zyy@sioc.ac.cn
lab head
Jing Gao
contact affiliation	Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry
contact email	gaojing@sioc.ac.cn
dataset submitter

iProX dataset URI