PXD034797

PXD034797 is an original dataset announced via ProteomeXchange.

Title	Usp25-Erlin1/2 activity limits cholesterol flux to trigger TLR3 responses and restrict a broad range of viruses
Description	Reprogramming lipid metabolic pathways is a critical feature of activating immune responses to infection. However, how these reconfigurations are regulated, particularly during virus infections are poorly understood. Our previous screen to identify cellular deubiquitylases activated during influenza virus infection revealed Usp25 as a prominent hit. Here we show that Usp25-deleted cells display >10-fold increase in pathogenic influenza virus and SARS-CoV-2 production, which were rescued upon reconstitution with the wild-type, but not the catalytically deficient (C178S) variant. Proteomic analysis of Usp25 interactors revealed a strong association with Erlin1/2, which we confirmed as its substrate. Newly synthesized Erlin1/2 were degraded in Usp25 -/- or Usp25 C178S cells, activating Srebp2, with concomitant increase in cholesterol efflux, LC3+ and Rab11+ compartments, and attenuated TLR3-dependent responses. In contrast, depletion of Smurf1, an E3 ligase, triggered Usp25 degradation and rescued this effect. Smurf1-deficient cells were refractory to infection by various pathogenic viruses, (e.g. SARS-CoV-2, H5N1 and H7N9) and induced robust Type I interferon response. Our study therefore defines the function of a deubiquitylase that serves to restrict a broad range of viruses by reprogramming lipid biosynthetic flux to install appropriate inflammatory responses.
HostingRepository	PRIDE
AnnounceDate	2026-02-09
AnnouncementXML	Submission_2026-02-08_16:18:15.860.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sumana Sanyal
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Influenza A virus; NCBI TaxID: NCBITaxon:11320;
ModificationList	iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-21 09:07:45	ID requested
⏵ 1	2026-02-08 16:18:20	announced

10.1016/j.devcel.2023.08.013;

Teo QW, Wong HH, Heunis T, Stancheva V, Hachim A, Lv H, Siu L, Ho J, Lan Y, Mok CKP, Ulferts R, Sanyal S, Usp25-Erlin1/2 activity limits cholesterol flux to restrict virus infection. Dev Cell, 58(22):2495-2509.e6(2023) [pubmed]

submitter keyword: Deubiquitylases, Lipid metabolism, Interaction proteomics,Antiviral immunity

Sumana Sanyal
contact affiliation	Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK
contact email	sumana.sanyal@path.ox.ac.uk
lab head
Sumana Sanyal
contact affiliation	University of Oxford
contact email	sumana.sanyal@path.ox.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD034797
     1. Label: PRIDE project
     2. Name: Usp25-Erlin1/2 activity limits cholesterol flux to trigger TLR3 responses and restrict a broad range of viruses