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PXD077990-1

PXD077990 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe deubiquitinase USP4 stabilizes the SCFFBXO24 ubiquitin E3 ligase to regulate immunity in experimental pneumonia
DescriptionThe ubiquitin E3 ligase SCFFBXO24 targets key proteins for degradation that regulate important biological processes, but the mechanisms controlling cellular concentrations of its receptor subunit, F-box only protein 24 (FBXO24), remain unknown. Here, Haemophilus influenzae type B (HiB), an important cause of pneumonia, protects FBXO24 from lysosomal degradation in THP-1 macrophage cells by reducing its ubiquitylation levels. We identified that the ubiquitin-specific peptidase 4 (USP4) mediates FBXO24 deubiquitylation and stabilization in response to HiB infection in a TLR4 receptor-dependent manner. In experimental HiB pneumonia, either nanoparticle delivery of encapsulated USP4 siRNA or targeted genetic disruption of Fbxo24 in mice led to increased alveolar mononuclear cells coupled with reduced bacterial loads, attenuated pulmonary edema and decreased lung injury severity compared to control mice. Collectively, these findings are the first demonstrating ability of a bacterial pathogen to exploit a deubiquitylation mechanism to preserve cellular levels of an E3 ligase component, thereby impairing innate host defense responses.
HostingRepositoryPRIDE
AnnounceDate2026-08-14
AnnouncementXMLSubmission_2026-08-14_08:06:18.441.xml
DigitalObjectIdentifierhttps://doi.org/10.6019/PXD077990
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterilknur Yurtsever
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListubiquitination signature dipeptidyl lysine
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-05-04 13:29:03ID requested
12026-08-14 08:06:18announced
Publication List
10.1038/S41467-026-75336-7;
10.6019/PXD077990;
Keyword List
submitter keyword: USP4, deubiquitylation, Haemophilus influenzae,FBXO24
Contact List
Rama K. Mallampalli
contact affiliationDepartment of Internal Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Davis Heart and Lung Institute, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
contact emailRama.Mallampalli2@osumc.edu
lab head
ilknur Yurtsever
contact affiliationPulmonary Crıtıcal Care, Sleep, Wexner Medical Center, Ohio State University
contact emailyurt02@osumc.edu
dataset submitter
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Dataset FTP location
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