PXD003637

PXD003637 is an original dataset announced via ProteomeXchange.

Title	TAILS proteomics of murine pancreatic tumors
Description	Aberrant proteolysis by cysteine cathepsins is implicated in carcinogenesis, but knowledge of cathepsin substrates mediating tumor-promoting or suppressing effects is limited. Here we characterize tumor proteome and in vivo cathepsin substrates using cathepsin knockout mice and the RIP1-Tag2 model of pancreatic islet carcinogenesis. Applying an unbiased systems-level proteomics approach, Terminal Amine Isotopic Labeling of Substrates (TAILS), we identified cysteine cathepsin B, H, L, S, Z substrates and their cleavage sites. Among 1,935 proteins and 1,114 N-termini identified by TAILS using 8-plex iTRAQ protein labeling, 145 neo-N-termini were significantly changed in one (55%) or more knockouts suggesting a lack of direct compensation at substrate level by other cathepsins. Most affected N-termini (56-83% for different cathepsins) represented degradative cathepsin activity, whereas 17-44% of neo-N termini represented stable proteolytic products in the tumors and were enriched for extracellular proteins. We identified candidate substrates for mediating signaling roles of cysteine cathepsins in tumorigenesis.
HostingRepository	PRIDE
AnnounceDate	2016-08-08
AnnouncementXML	Submission_2016-08-08_03:32:38.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	iTRAQ8plex-116 reporter+balance reagent acylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	QSTAR

Revision	Datetime	Status	ChangeLog Entry
0	2016-02-15 05:27:36	ID requested
⏵ 1	2016-08-08 03:32:40	announced

Prudova A, Gocheva V, Auf dem Keller U, Eckhard U, Olson OC, Akkari L, Butler GS, Fortelny N, Lange PF, Mark JC, Joyce JA, Overall CM, TAILS N-Terminomics and Proteomics Show Protein Degradation Dominates over Proteolytic Processing by Cathepsins in Pancreatic Tumors. Cell Rep, 16(6):1762-1773(2016) [pubmed]

curator keyword: Biomedical

submitter keyword: Pancreatic neuroendocrine cancer, cysteine cathepsins, TAILS N-terminomics, substrate discovery, proteolytic processing, degradation, proteases, proteomics, ECM

Christopher M. Overall
contact affiliation	University of British Columbia
contact email	chris.overall@ubc.ca
lab head
Ulrich auf dem Keller
contact affiliation	Department of Biology
contact email	ulrich.aufdemkeller@biol.ethz.ch
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/2016/08/PXD003637

PRIDE project URI

• PRIDE
  1. PXD003637
     1. Label: PRIDE project
     2. Name: TAILS proteomics of murine pancreatic tumors