PXD030939

PXD030939 is an original dataset announced via ProteomeXchange.

Title	A compound-based therapy approach for epidermolysis bullosa simplex (EBS)
Description	Keratin cytoskeletal proteins are crucial for the maintenance of skin integrity. Mutations in genes coding for K5 and K14 cause the human skin disorder epidermolysis bullosa simplex (EBS) leading to substantial alterations in keratin assembly and collapse of keratin filaments into cytoplasmic protein aggregates. The phenotypic consequences of K5 and K14 mutations comprise fragility of basal keratinocytes and skin blistering upon mild mechanical trauma. Treatment of EBS is only supportive and consists primarily of wound care and avoidance of mechanical stress. Besides symptomatic care, no efficient therapeutic treatment is available for EBS. In the present study, we used patient-derived keratinocytes carrying the most frequent K14.R125C mutation as a reproducible EBS model to understand EBS pathomechanisms and to develop a therapy approach aimed to restore a functional keratin network. Numerous post-translational modifications (PTMs) such as phosphorylation have been reported to occur on keratins, which affect the organization of keratin networks. Whether keratin mutations affect the occurrence of PTMs and thereby keratin aggregation in EBS is yet unknown. We find that the K14.R125C mutation alters keratin and keratin-associated protein PTMs in distinct ways and suggest that disease mutations and altered PTMs aggravate keratin aggregation. We reason that chemical compounds affecting the interplay of mutations and PTMs enable the reformation of a keratin cytoskeleton from aggregates are potential candidates for combating EBS.
HostingRepository	PRIDE
AnnounceDate	2022-06-29
AnnouncementXML	Submission_2022-06-29_00:13:45.658.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Prerana Wagle
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-13 07:54:06	ID requested
⏵ 1	2022-06-29 00:13:46	announced

Dataset with its publication pending

submitter keyword: Keratins, epidermolysis bullosa simplex, multi-kinase inhibitor, phosphorylation, therapy

Carien M. Niessen
contact affiliation	Department Cell Biology of the Skin, Cologne Excellence Cluster for Stress Responses in Ageing-associated diseases (CECAD), Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne 50931, Germany
contact email	carien.niessen@uni-koeln.de
lab head
Prerana Wagle
contact affiliation	CECAD Research Center
contact email	proteomics-facility@uni-koeln.de
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/2022/06/PXD030939

PRIDE project URI

• PRIDE
  1. PXD030939
     1. Label: PRIDE project
     2. Name: A compound-based therapy approach for epidermolysis bullosa simplex (EBS)