PXD067480

PXD067480 is an original dataset announced via ProteomeXchange.

Title	Proteomics Reveals Altered Lipid Biosynthesis and Keratin Hyperphosphorylation in Pachyonychia Congenita
Description	Pachyonychia congenita (PC) is a rare and painful skin disorder caused by dominant mutations in keratin genes (KRT6A/KRT6B/KRT6C/KRT16/KRT17), with no effective treatment. We developed a scalable, in-depth and miniaturized MS-based proteomics and phospho-proteomics analysis of full-thickness skin biopsies applied to 10 PC patients to elucidate pathogenic mechanisms and pinpoint new therapeutic targets. We could quantify 7200 Protein Groups (PGs), on average from 2mm snap-frozen skin samples, the most in-depth proteome coverage reported to date in a single-shot MS analysis. Among the identified PGs, ~1400 proteins were significantly deregulated in lesional vs. non-lesional samples. Enrichment analysis points to impaired mitochondrial function, hyper-keratinization, enhanced immune response and a significant increase in cholesterol biosynthesis pathway. Phosphoproteomics study revealed hyper-phosphorylation of specific sites in PC-related keratins. It confirmed the activation of EGFR downstream kinases, including PKC and Src, and disclosed p38 MAPK activation, which have been reported to phosphorylate keratins. Our work expands the understanding of the consequences of EGFR pathway activation, including mTOR-dependent increase in cholesterol biosynthesis, thereby renewing interest in the use of statins for PC. Above all, it provides a solid foundation for the continued exploration of EGFR inhibitors and offers new therapeutic avenues, particularly those using multikinase inhibitors.
HostingRepository	PRIDE
AnnounceDate	2026-01-14
AnnouncementXML	Submission_2026-01-14_06:02:28.624.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chiara guerrera
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-18 10:24:36	ID requested
⏵ 1	2026-01-14 06:02:29	announced

Dataset with its publication pending

submitter keyword: proteomics, skin, keratins,Pachyonychia Congenita, phosphoproteomics

Ida Chiara Guerrera
contact affiliation	Proteomics platform Necker, Université Paris Cité - Structure Fédérative de Recherche Necker, INSERM US24/CNRS UAR3633, Paris 75015, France
contact email	chiara.guerrera@inserm.fr
lab head
Chiara guerrera
contact affiliation	Necker proteomics, INSERM
contact email	chiara.guerrera@inserm.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/01/PXD067480

PRIDE project URI

• PRIDE
  1. PXD067480
     1. Label: PRIDE project
     2. Name: Proteomics Reveals Altered Lipid Biosynthesis and Keratin Hyperphosphorylation in Pachyonychia Congenita