PXD007049-1

PXD007049 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 complexes1, have been recently associated with Noonan syndrome2,3 and familial Schwannomatosis4-6. 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. We screened for LZTR1 substrates by trapping LZTR1 complexes from intact mammalian cells. In parallel, we analysed changes in the ubiquitin landscape induced by LZTR1 loss of function. RAS proteins emerged as substrates of the LZTR1/CUL3 complex, which 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. These results position LZTR1 as a key node in the RAS pathway, loss-of-function of which leads to a human disease.
HostingRepository	PRIDE
AnnounceDate	2018-11-04
AnnouncementXML	Submission_2018-11-04_15:35:54.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sven Eyckerman
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-07-14 04:21:22	ID requested
⏵ 1	2018-11-04 15:35:55	announced
2	2024-10-22 04:39:35	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: VIROTRAP Protein complex

Sven Eyckerman
contact affiliation	VIB-UGent Center for Medical Biotechnology
contact email	sven.eyckerman@vib-ugent.be
lab head
Sven Eyckerman
contact affiliation	Medical Protein Research
contact email	sven.eyckerman@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/PXD007049

PRIDE project URI

• PRIDE
  1. PXD007049
     1. Label: PRIDE project
     2. Name: Loss-of-function of ubiquitin ligase adaptor LZTR1 triggers human disease by dysregulating RAS ubiquitination