PXD002597

PXD002597 is an original dataset announced via ProteomeXchange.

Title	The Skin Barrier Defects Caused by Keratinocyte-Specific Deletion of ADAM17 or EGFR are Based on Highly Similar Proteome and Degradome Alterations
Description	ADAM17 and EGFR are essential key players for epidermal integrity. Keratinocyte-specific deletion of ADAM17 in mice results in pronounced alterations in terminal differentiation of keratinocytes leading to severe epidermal barrier defects with enhanced transepidermal water loss. Thereby, mice deficient for ADAM17 in keratinocytes phenocopy mice with a keratinocyte-specific deletion of EGFR, highlighting the role of ADAM17 as a “ligand sheddase”, as it sheds membrane bound EGFR ligands from the cell surface and finally modulates EGFR signaling. In this study we aim for the first proteomic / degradomic approach to characterize the disruption of the ADAM17-EGFR signaling axis and its consequences for epidermal barrier formation. Proteomic profiling of the epidermal proteome of mice deficient for either ADAM17 or EGFR in keratinocytes at postnatal days 3 and 10 revealed highly similar protein alterations for ADAM17 and EGFR deficiency. These include massive proteome alterations of structural and regulatory components important for barrier formation, like transglutaminases, involucrin, S100 protein family members and S100 fused-type proteins, such as filaggrin, filaggrin-2 and hornerin. Cleavage site analysis using TAILS reveals, among other ADAM17 dependent cleavage sites, increased proteolytic processing of S100 fused-type proteins, including filaggrin-2. Alterations in proteolytic processing are supported by altered protein abundance of numerous proteases upon keratinocyte-specific Adam17 or Egfr deletion, among them kallikreins, cathepsins and their inhibitors. In addition, N-terminal proteomics indicated usage of alternative translation start sites. This study highlights the essential role of proteolytic processing for maintenance of a functional epidermal barrier. Furthermore it suggests that most defects in formation of the postnatal epidermal barrier upon keratinocyte-specific ADAM17 deletion are mediated via EGFR.
HostingRepository	PRIDE
AnnounceDate	2016-04-20
AnnouncementXML	Submission_2016-04-20_09:54:11.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stefan Tholen
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2015-07-24 03:28:56	ID requested
⏵ 1	2016-04-20 09:54:12	announced

Tholen S, Wolf C, Mayer B, Knopf JD, L, ö, ffek S, Qian Y, Kizhakkedathu JN, Biniossek ML, Franzke CW, Schilling O, Skin Barrier Defects Caused by Keratinocyte-Specific Deletion of ADAM17 or EGFR Are Based on Highly Similar Proteome and Degradome Alterations. J Proteome Res, 15(5):1402-17(2016) [pubmed]

curator keyword: Biomedical, Biological

submitter keyword: proteomics, degradomics, skin

Oliver Schilling
contact affiliation	Institute of Molecular Medicine and Cell Research University of Freiburg Stefan Meier Strasse 17 79104 Freiburg, Germany
contact email	oliver.schilling@mol-med.uni-freiburg.de
lab head
Stefan Tholen
contact affiliation	Institute for Molecular Medicine
contact email	stefan.tholen@mol-med.uni-freiburg.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/2016/04/PXD002597

PRIDE project URI

• PRIDE
  1. PXD002597
     1. Label: PRIDE project
     2. Name: The Skin Barrier Defects Caused by Keratinocyte-Specific Deletion of ADAM17 or EGFR are Based on Highly Similar Proteome and Degradome Alterations