PXD043536 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Proteomic mapping of the interactome of KRAS mutants identifies new features of RAS signalling networks and the mechanism of action of Sotorasib. |
Description | RAS proteins are key regulators of cell signalling and are master regulators of different cell functions including cell proliferation, differentiation and cell death. Point mutations in the genes of this family are common, particularly in the KRAS. These mutations were thought to cause the constative activation of KRAS, but recent findings showed that some of these mutants can still cycle between active and inactive states. This observation together with the development of covalent KRASG12C inhibitors has led to the arrival to the clinic of KRAS inhibitors. However, most patients develop resistance to these targeted therapies, and we still lack effective treatments for other KRAS mutants. In order to accelerate the development of RAS targeting therapies we need to complete our characterisation of the molecular mechanisms that govern KRAS signalling networks and in particular determine if there are differences among the different KRAS mutants. Here we have used affinity purification mass-spectrometry proteomics to characterise the interactome of KRAS wild type and three KRAS mutants. Bioinformatic analysis associated with experimental validation allow us to map the signalling network mediated by the different KRAS proteins. Using this approach, we have also characterised the effect that clinically approved KRASG12 inhibitor sotorasib has in the interactome of these mutants and KRAS wild type. Our work indicates that this drug regulates the interactome and identifies new crosstalks between KRAS and its effector pathways including the AKT and JAK-STAT signalling modules. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:05:59.303.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Kieran Wynne |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | timsTOF Pro |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-07-04 08:21:20 | ID requested | |
1 | 2023-10-15 12:04:15 | announced | |
2 | 2023-11-14 09:05:58 | announced | 2023-11-14: Updated project metadata. |
⏵ 3 | 2024-10-22 06:06:02 | announced | 2024-10-22: Updated project metadata. |
Publication List
10.3390/cancers15164141; |
Nolan A, Raso C, Kolch W, Kriegsheim AV, Wynne K, Matallanas D, Proteomic Mapping of the Interactome of KRAS Mutants Identifies New Features of RAS Signalling Networks and the Mechanism of Action of Sotorasib. Cancers (Basel), 15(16):(2023) [pubmed] |
Keyword List
submitter keyword: APMS,RAS, Signalling |
Contact List
David Gomez |
contact affiliation | Systems Biology Ireland University College Dublin. |
contact email | david.gomez@ucd.ie |
lab head | |
Kieran Wynne |
contact affiliation | University College Dublin |
contact email | kieran.wynne1@ucd.ie |
dataset submitter | |
Full Dataset Link List
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/2023/10/PXD043536 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD043536
- Label: PRIDE project
- Name: Proteomic mapping of the interactome of KRAS mutants identifies new features of RAS signalling networks and the mechanism of action of Sotorasib.