PXD066221-1

PXD066221 is an original dataset announced via ProteomeXchange.

Title	Long-chain S-acylation is a key modulator during the macrophage inflammatory response
Description	Long-chain S-acylation is a reversible lipid modification critical for regulating protein localization, stability, and signaling, yet its role in macrophage-mediated inflammation remains incompletely understood. Here, we combine stable isotope labeling by amino acids in cell culture (SILAC) with site-specific acyl-biotin exchange (ssABE) to generate a comprehensive map of the long-chain S-acylation landscape in THP-1 macrophages polarized to M0 and M1 states. Our quantitative proteomics reveal polarization-specific S-acylation patterns and uncover numerous inflammation-induced modification sites, including novel S-acyl modiforms, which are distinct S-acylated variants of the same proteinsuch as WARS (C305/C309), highlighting their potential functional relevance in macrophage activation. Pharmacological inhibition of S-acylation with the broad-spectrum inhibitor 2-bromopalmitate suppresses secretion of key pro-inflammatory chemokines (CXCL9, CXCL10, CCL4) and disrupts IDO1-mediated tryptophan catabolism, while Palmostatin B stabilizes S-acylation mainly on GPCR signaling proteins as well as Toll-like receptor 1/6. Together, these findings position long-chain S-acylation as a key regulatory mechanism during macrophage activation, and a promising target for therapeutic intervention in inflammatory disease.
HostingRepository	PRIDE
AnnounceDate	2026-06-10
AnnouncementXML	Submission_2026-06-10_14:45:29.037.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Anneroos Nederstigt
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	N-ethylmaleimide derivatized cysteine; 6x(13)C; palmitoylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480; timsTOF HT

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-16 09:24:43	ID requested
⏵ 1	2026-06-10 14:45:29	announced
2	2026-06-10 15:00:36	announced	2026-06-10: Updated project metadata.

Dataset with its publication pending

submitter keyword: None

Marc Pieter
contact affiliation	Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, Utrecht 3584 CH, The Netherlands
contact email	m.p.baggelaar@uu.nl
lab head
Anneroos Nederstigt
contact affiliation	Biomolecular Mass Spectrometry and Proteomics, Bijvoet Centre for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht
contact email	a.e.nederstigt@uu.nl
dataset submitter

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://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD066221

PRIDE project URI

• PRIDE
  1. PXD066221
     1. Label: PRIDE project
     2. Name: Long-chain S-acylation is a key modulator during the macrophage inflammatory response