PXD000781

PXD000781 is an original dataset announced via ProteomeXchange.

Title	Huwe1-mediated ubiquitylation of Dvl defines a novel negative feedback loop in the Wnt signaling pathway
Description	Wnt signaling plays a central role in development, adult tissue homeostasis and cancer. Several steps in the canonical Wnt/b-catenin signaling cascade are regulated by ubiquitylation, a protein modification that influences the stability, subcellular localization or protein-protein interactions of target proteins. To identify novel regulators of the Wnt/b-catenin pathway, we performed RNAi screens in C. elegans and human tissue culture cells and identified the HECT domain containing ubiquitin ligase eel-1/Huwe1 as a negative regulator of Wnt signaling. Huwe1 functions cell autonomously in signal-receiving cells and genetically acts upstream of b-catenin. Mechanistically, Huwe1 binds to and ubiquitylates the cytoplasmic Wnt pathway component Dishevelled (Dvl) in a Wnt3a and CK1e dependent manner. Huwe1 mediated ubiquitylation does not target Dvl for degradation. Instead, we found that Huwe1 decreases Dvl signaling by inhibiting Dvl multimerization. We conclude that Huwe1 is part of an evolutionarily conserved negative feedback loop in the Wnt/b-catenin pathway
HostingRepository	PRIDE
AnnounceDate	2014-07-24
AnnouncementXML	Submission_2014-07-24_05:19:03.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD000781
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Katerina Sedova
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue; ubiquitination signature dipeptidyl lysine
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2014-02-28 02:26:11	ID requested
1	2014-05-28 00:45:01	announced
⏵ 2	2014-07-24 05:19:04	announced	Updated project metadata.

de Groot RE, Ganji RS, Bernatik O, Lloyd-Lewis B, Seipel K, Š, edov, á K, Zdr, á, hal Z, Dhople VM, Dale TC, Korswagen HC, Bryja V, Huwe1-mediated ubiquitylation of dishevelled defines a negative feedback loop in the Wnt signaling pathway. Sci Signal, 7(317):ra26(2014) [pubmed]

curator keyword: Biological

submitter keyword: ubiquitylation, Dvl, Wnt signaling

Zbynek Zdrahal
contact affiliation	Central European Institute of Technology, Masaryk University, Brno, Czech Republic National Centre for Biomolecular research, Masaryk University, Brno, Czech Republic
contact email	zdrahal@sci.muni.cz
lab head
Katerina Sedova
contact affiliation	Masaryk University
contact email	kaculen@seznam.cz
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/2014/05/PXD000781

PRIDE project URI

• PRIDE
  1. PXD000781
     1. Label: PRIDE project
     2. Name: Huwe1-mediated ubiquitylation of Dvl defines a novel negative feedback loop in the Wnt signaling pathway