PXD059785

PXD059785 is an original dataset announced via ProteomeXchange.

Title	STING Acts as a Rheostat of the Unfolded Protein Response to Regulate Antigen Presentation during Inflammation
Description	In addition to inflammation, a growing body of evidence supports the contribution of the long-lasting adaptive immune system in Parkinson’s disease (PD). We reported previously that, in inflammatory conditions, the PD-associated proteins PINK1 and Parkin negatively regulate the presentation of mitochondrial antigens on MHC-I molecules, a process referred to as MitAP (Mitochondrial Antigen Presentation). In vitro and in vivo evidence in mice indicated that over-activation of MitAP, in the absence of PINK1, led to cytotoxic CD8+ T cell activation with attack on dopaminergic neurons and severe motor impairments reversible by L-DOPA. The molecular mechanisms regulating MitAP are poorly understood. We show here that the TRAM/TRIF arm of Toll-like receptor 4 (TLR4) triggers MitAP through a non-canonical pathway involving TBK1 but not IRF3. The cGAS-STING pathway plays a key role in MitAP through a small cytoplasmic domain, enabling STING to act as a rheostat to control the unfolded protein response (UPR). In the absence of STING, the UPR triggered during the inflammatory response is amplified, leading to a translational attenuation inhibiting the expression of XBP1s, a transcription factor required for MitAP. STING also broadly regulates the repertoire of peptides displayed at the cell surface during inflammation, highlighting a potential role in immunosurveillance. These findings establish STING as a key regulator coordinating the innate and adaptive immune response in inflammatory conditions, identifying the cGAS-STING pathway and the UPR as potential targets for therapeutic intervention during PD.
HostingRepository	PRIDE
AnnounceDate	2025-01-22
AnnouncementXML	Submission_2025-01-22_05:12:55.674.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD059785
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Eric Bonneil
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-14 08:11:15	ID requested
⏵ 1	2025-01-22 05:12:56	announced

10.6019/PXD059785;

submitter keyword: mitochondrail antigen presentation, STING,Parkinson's disease, inflammation, immunopeptidomics

Michel Desjardins
contact affiliation	Université de Montréal
contact email	michel.desjardins@umontreal.ca
lab head
Eric Bonneil
contact affiliation	Proteomic Platform
contact email	eric.bonneil@umontreal.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059785
     1. Label: PRIDE project
     2. Name: STING Acts as a Rheostat of the Unfolded Protein Response to Regulate Antigen Presentation during Inflammation