PXD002474

PXD002474 is an original dataset announced via ProteomeXchange.

Title	MMP10 degradomics in keratinocytes
Description	Matrix metalloproteinases (MMPs) are important players in skin homeostasis, wound repair, and in the pathogenesis of skin cancer. One member – MMP10 – is specifically expressed in wound keratinocytes and in epithelial cancer cells, but its function is unclear and epidermal substrates are poorly characterized. To unravel the role of MMP10 in the skin, we employed Terminal Amine Isotopic Labeling of Substrates (TAILS), an iTRAQ-based quantitative proteomics technique for the discovery of protease substrates and their cleavage sites, to monitor MMP10-dependent proteolysis over time in secretomes from keratinocytes. By time-resolved abundance clustering of neo-N termini we revealed a cleavage site specificity preference of MMP10 for glutamate in the P1 position and identified the α6 integrin subunit, cysteine-rich angiogenic inducer 61 and dermokine as novel MMP10 substrates. Moreover, we confirmed the same MMP10-dependent processing of dermokine in vivo by TAILS analysis of epidermis from transgenic mice that overexpress a constitutively active mutant of MMP10 in basal keratinocytes. Since these substrates have been associated with cell adhesion, differentiation and senescence, MMP10 might contribute to modulation of these processes during skin repair.
HostingRepository	PRIDE
AnnounceDate	2015-10-19
AnnouncementXML	Submission_2015-10-19_04:56:41.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ulrich auf dem Keller
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	2-pyrrolidone-5-carboxylic acid (Glu); monohydroxylated residue; iTRAQ8plex-116 reporter+balance reagent acylated residue; acetylated residue; iTRAQ4plex-116 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2015-07-03 08:16:46	ID requested
⏵ 1	2015-10-19 04:56:42	announced

Schlage P, Kockmann T, Sabino F, Kizhakkedathu JN, Auf dem Keller U, Matrix Metalloproteinase 10 Degradomics in Keratinocytes and Epidermal Tissue Identifies Bioactive Substrates With Pleiotropic Functions. Mol Cell Proteomics, 14(12):3234-46(2015) [pubmed]

curator keyword: Biomedical, Biological

submitter keyword: iTRAQ-TAILS, MMP10, degradomics, skin, keratinocytes

Ulrich auf dem Keller
contact affiliation	Institute of Molecular Health Sciences, Department of Biology, ETH Zurich
contact email	ulrich.aufdemkeller@biol.ethz.ch
lab head
Ulrich auf dem Keller
contact affiliation	Department of Biology
contact email	ulrich.aufdemkeller@biol.ethz.ch
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002474
     1. Label: PRIDE project
     2. Name: MMP10 degradomics in keratinocytes