PXD069750-1

PXD069750 is an original dataset announced via ProteomeXchange.

Title	Nuclear RSK1 mediates interferon γ-induced pro-inflammatory activation in human primary macrophages and humanized mice
Description	Pro-inflammatory activation of macrophages promotes various inflammatory disorders. The molecular mechanisms underlying macrophage activation, particularly in the context of nuclear translocation of pro-inflammatory response mediators, remain obscure. We have used a systems approach to explore key regulators of macrophage activation using quantitative proteomics to monitor protein translocation to the nuclei of human primary macrophages elicited with interferon γ (IFN-γ). Unbiased bioinformatics identified several candidates, including RSK1, a ribosomal protein kinase. Network analysis linked RSK1 with human gene modules for various inflammatory disorders. In vitro mechanistic experiments showed that IFN-γ stimulation promotes RSK1 phosphorylation at Ser380 via JAK signaling, resulting in STAT1 phosphorylation at Ser727, in the nuclei of macrophages. In concert with these results, RSK1 silencing or deficiency hinders IFN-γ-induced secretion of pro-inflammatory chemokines in human primary macrophages. Furthermore, RSK1 deficiency in human leukocytes altered IFN-γ-induced responses in humanized mice. Our findings provide evidence that RSK1 is a key nuclear shuttling enzyme that mediates pro-inflammatory activation of macrophages.
HostingRepository	PRIDE
AnnounceDate	2026-07-08
AnnouncementXML	Submission_2026-07-08_14:50:24.012.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sasha Singh
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2025-10-21 19:40:20	ID requested
⏵ 1	2026-07-08 14:50:24	announced

10.1126/SCIADV.ADY4193;

submitter keyword: PBMC,RSK1, macrophage, humanized mice, IFNg

Masanori Aikawa
contact affiliation	Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, U.S.A.
contact email	MAIKAWA@bwh.harvard.edu
lab head
Sasha Singh
contact affiliation	Brigham and Women's Hospital, Harvard Medical School
contact email	sasingh@bwh.harvard.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD069750
     1. Label: PRIDE project
     2. Name: Nuclear RSK1 mediates interferon γ-induced pro-inflammatory activation in human primary macrophages and humanized mice