PXD007035

PXD007035 is an original dataset announced via ProteomeXchange.

Title	Loss-of-function of ubiquitin ligase adaptor LZTR1 triggers human disease by dysregulating RAS ubiquitination
Description	Mutations in LZTR1, a substrate adaptor for cullin 3 (CUL3) ubiquitin ligase complexes, have been recently associated with Noonan syndrome and familial Schwannomatosis. Concordantly, we found that Lztr1+/- mice showed craniofacial abnormalities, cardio defects, and premature ageing; whereas loss of LZTR1 in Schwann cells drives their dedifferentiation into proliferating, pro-myelinating cells. In the present dataset we screened for changes in the ubiquitin landscape induced by LZTR1 loss of function by mass spectrometry-based proteomics and identified RAS proteins as substrates of the LZTR1/CUL3 complex. In follow-up experiments we showed that LZTR1/CUL3 inhibits the RAS pathway by ubiquitinating RAS at K170 and triggering its dissociation from the membrane. Disease-associated LZTR1 mutations affect either the LZTR1/CUL3 complex formation, or the interaction with RAS proteins. Together, our results position LZTR1 as a key node in the RAS pathway, loss-of-function of which leads to human disease.
HostingRepository	PRIDE
AnnounceDate	2018-11-07
AnnouncementXML	Submission_2018-11-07_02:12:46.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Impens Francis
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	ubiquitination signature dipeptidyl lysine; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF; LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2017-07-13 00:24:20	ID requested
⏵ 1	2018-11-07 02:12:46	announced

Dataset with its publication pending

submitter keyword: RAS signalling, ubiquitin, schwannomatosis, Noonan syndrome

Anna A Sablina
contact affiliation	VIB-KU Leuven Center for Cancer Biology, VIB, Leuven, Belgium Department of Oncology, KU Leuven, Herestraat 49, Leuven, Belgium
contact email	anna.sablina@kuleuven.vib.be
lab head
Impens Francis
contact affiliation	VIB Proteomics Expertise Center
contact email	francis.impens@vib-ugent.be
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/2018/11/PXD007035

PRIDE project URI

• PRIDE
  1. PXD007035
     1. Label: PRIDE project
     2. Name: Loss-of-function of ubiquitin ligase adaptor LZTR1 triggers human disease by dysregulating RAS ubiquitination