PXD046284-1

PXD046284 is an original dataset announced via ProteomeXchange.

Title	MOF-mediated PRDX1 acetylation regulates inflammatory macrophage activation
Description	Macrophage activation undergoes signal-transduced changes in protein modifications, enabling the coordinated control of transcription and cellular metabolism. However, the role of protein acetylation in signal transduction during macrophage activation remains obscure. Here, we demonstrate that peroxiredoxin 1 (PRDX1), a key regulator of redox signaling, is a novel substrate of the MOF lysine acetyltransferase. Employing a gel based in vitro HAT assay followed by LC-MS, we mapped PRDX1 lysine acetylation sites. PRDX1 K197ac was identified as the most prominent MOF acetylation site. We show that MOF-dependent acetylation of lysine 197 of PRDX1 (PRDX1 K197ac) enhances its peroxidase activity. We find that PRDX1 K197ac is an inflammatory signal-regulated modification, which decreases in mouse macrophages stimulated with bacterial lipopolysaccharides (LPS) but not with IL-4 or IL-10. LPS-induced decrease of PRDX1 K197ac elevates cellular ROS accumulation and augments phosphorylation of ERK1/2 but not p38 or AKT phosphorylation. Concomitantly, diminished PRDX1 K197ac stimulates glycolysis, potentiates H3 serine 28 phosphorylation, and ultimately enhances the production of pro-inflammatory mediators such as IL-6. Collectively, our findings uncover a regulatory role for redox protein acetylation during inflammatory macrophage activation through modulating signal transduction and coordinating metabolic and transcriptional programs.
HostingRepository	PRIDE
AnnounceDate	2024-10-25
AnnouncementXML	Submission_2024-10-25_01:58:54.030.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gerhard Mittler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2023-10-22 04:20:49	ID requested
⏵ 1	2024-10-25 01:58:54	announced

10.1016/J.CELREP.2024.114682;

submitter keyword: lysine acetylation, HEK,Histone acetyl transferase, macrophage, PRDX1, MOF/KAT8, LC-MS, Gel based MS, LFQ

Gerhard Mittler
contact affiliation	Proteomics Unit Max Planck Institute of Immunobiology and Epigenetics Stuebeweg 51 79108 Freiburg, Germany
contact email	mittler@ie-freiburg.mpg.de
lab head
Gerhard Mittler
contact affiliation	Proteomics Unit, Max Planck Institute of Immunobiology and Epigenetics
contact email	mittler@ie-freiburg.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD046284
     1. Label: PRIDE project
     2. Name: MOF-mediated PRDX1 acetylation regulates inflammatory macrophage activation