PXD007035 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2017-07-13 00:24:20 | ID requested | |
⏵ 1 | 2018-11-07 02:12:46 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: RAS signalling, ubiquitin, schwannomatosis, Noonan syndrome |
Contact List
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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD007035
- Label: PRIDE project
- Name: Loss-of-function of ubiquitin ligase adaptor LZTR1 triggers human disease by dysregulating RAS ubiquitination