PXD007947

PXD007947 is an original dataset announced via ProteomeXchange.

Title	USP7 is a tumor-specific WNT activator for APC-mutated colorectal cancer by mediating B-catenin deu
Description	The tumor suppressor gene adenomatous polyposis coli (APC) is mutated in most colorectal cancers (CRC) resulting in constitutive Wnt activation. To understand the Wnt-activating mechanism of APC mutation, we applied CRISPR/Cas9 technology to engineer various APC-truncated isogenic lines. We find that the β-catenin inhibitory domain (CID) in APC represents the threshold for pathological levels of Wnt activation and tumor transformation. Mechanistically, CID-deleted APC truncation promotes β-catenin deubiquitination through reverse binding of β-TrCP and USP7 to the destruction complex. USP7 depletion in APC-mutated CRC inhibits Wnt activation by restoring β-catenin ubiquitination, drives differentiation and suppresses xenograft tumor growth. Finally, the Wnt-activating role of USP7 is specific to APC mutations, thus can be used as tumor-specific therapeutic target for most CRCs.
HostingRepository	PRIDE
AnnounceDate	2017-11-09
AnnouncementXML	Submission_2017-11-09_03:58:07.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Jones
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2017-10-11 08:34:49	ID requested
⏵ 1	2017-11-09 03:58:08	announced

Novellasdemunt L, Foglizzo V, Cuadrado L, Antas P, Kucharska A, Encheva V, Snijders AP, Li VSW, -Catenin Deubiquitination. Cell Rep, 21(3):612-627(2017) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: APC, LFQ

Bram Snijders
contact affiliation	The Francis Crick Institute, Mass Spectrometry Science Technology Platform
contact email	Bram.Snijders@crick.ac.uk
lab head
Andrew Jones
contact affiliation	The Francis Crick Institute
contact email	Andrew.Jones@crick.ac.uk
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/2017/11/PXD007947

PRIDE project URI

• PRIDE
  1. PXD007947
     1. Label: PRIDE project
     2. Name: USP7 is a tumor-specific WNT activator for APC-mutated colorectal cancer by mediating B-catenin deu