PXD036627-1

PXD036627 is an original dataset announced via ProteomeXchange.

Title	IKKα dependent activation of the β-catenin pathway is required for endosomal maturation and SARS-CoV-2 entry
Description	COVID-19 is a complex disease characterized by fulminant replication of SARS-CoV-2 and associated virus-induced comorbidities. While the virus impedes induction and activity of host-protective antiviral processes, it at the same time induces exacerbated expression and function of NF-κB dependent inflammatory cytokines, leading to a hyperinflammatory syndrome associated with viral pathology. Here we identified a yet uncharacterized link between components of the NF-κB pathway and the maturation of endolysosomes, which is essential for SARS-CoV-2 entry. Chemical inhibition or genetic ablation of IKKα and NIK kinases prevents virus infection while other downstream components of the NF-κB signaling cascade are dispensable. Notably, IKKα is required for acidification of intracellular vesicles, which is an essential step in the SARS-CoV-2 infection process and inhibition of this kinase traps SARS-CoV-2 in endolysosomal compartments. Phosphoproteomic and transcriptomic analysis identified an unexpected link between IKKα and activation of the β-catenin pathway, which is known for its involvement in promoting the endosomal pathway. We propose that the aggravated NF-κB response, which is prominently observed in COVID-19 patients, facilitates SARS-CoV-2 infection through increased IKKα activity. Notably, although we identified this pathway to be essential for SARS-CoV-2 entry, we demonstrate that the activity IKKα is generally required for full maturation of endolysosomes.
HostingRepository	PRIDE
AnnounceDate	2026-08-03
AnnouncementXML	Submission_2026-08-03_04:20:14.076.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Quirin Emslander
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606; scientific name: Severe acute respiratory syndrome coronavirus 2; NCBI TaxID: NCBITaxon:2697049;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-12 03:56:12	ID requested
⏵ 1	2026-08-03 04:20:14	announced

Dataset with its publication pending

ProteomeXchange project tag: Sars-cov-2, Covid-19

submitter keyword: NFKB, SARS-Cov-2, phosphoproteomics,shotgun proteomics

Andreas Pichlmair
contact affiliation	Immunopathology of Virus Infections, Technical University of Munich, School of Medicine, Institute of Virology, 81675 Munich, Germany
contact email	andreas.pichlmair@tum.de
lab head
Quirin Emslander
contact affiliation	TUM
contact email	quirin.emslander@tum.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036627
     1. Label: PRIDE project
     2. Name: IKKα dependent activation of the β-catenin pathway is required for endosomal maturation and SARS-CoV-2 entry