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PXD070618-1

PXD070618 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePCK2-mediated PQBP1 lactylation promotes asthmatic inflammation through PRMT5 inhibition
DescriptionBackground: Asthma involves chronic inflammation linked to metabolic reprogramming, but how metabolites reshape epigenetics through post-translational modifications remains unclear. Methods: We used HDM-induced asthmatic mice with multi-omics analyses (metabolomics, PTM-proteomics, ChIP-seq) and validated findings through gene editing and AAV interventions. Results: Asthmatic airways showed lactate-driven glutaminolysis, causing lactate/succinate accumulation. PCK2 succinylation at K100 enhanced stability by antagonizing ubiquitination, creating a lactate-generating feedback loop. Accumulated lactate triggered PQBP1 lactylation at K223, enabling PRMT5/WDR77 complex inhibition. This erased H4R3me2s repressive marks from pro-inflammatory gene promoters, particularly MAPK pathway genes, causing transcriptional de-repression. Airway epithelium-specific PQBP1 knockout reduced inflammation, goblet cell hyperplasia, and Th2 responses. PCK2-shRNA or oxamate treatment ameliorated asthmatic pathology. Conclusion: We identified a PCK2-lactate-PQBP1-PRMT5 axis linking metabolic reprogramming to epigenetic dysregulation in asthma. PCK2-K100 succinylation drives lactate accumulation, inducing PQBP1-K223 lactylation that inhibits PRMT5 and activates inflammatory genes, representing a therapeutic target for asthma.
HostingRepositoryiProX
AnnounceDate2025-11-12
AnnouncementXMLSubmission_2025-11-11_19:05:35.975.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGuanghai Yan
SpeciesList scientific name: Homo sapiens; NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumenttimsTOF Pro
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-11-11 19:05:10ID requested
12025-11-11 19:05:36announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: Asthma, Lactylation, Succinylation
Contact List
Guanghai Yan
contact affiliationDepartment of Anatomy, Histology and Embryology, Yanbian University Medical College
contact emailghyan@ybu.edu.cn
lab head
Guanghai Yan
contact affiliationDepartment of Anatomy, Histology and Embryology, Yanbian University Medical College
contact emailghyan2015@sina.com
dataset submitter
Full Dataset Link List
iProX dataset URI