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PXD035399

PXD035399 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAnalysis of context-specific KRAS-effectors (sub)complexes in Caco-2 cells
DescriptionRas is a key switch controlling cell behavior. In the GTP-bound form, Ras interacts with numerous effectors in a mutually exclusive manner, where individual Ras-effectors are likely part of larger cellular (sub)complexes. The molecular details of these (sub)complexes and their alteration in specific contexts is not understood. Focusing on KRAS, we performed affinity purification (AP)-mass spectrometry (MS) experiments of exogenous expressed Flag-KRAS WT and three oncogenic mutants (‘genetic contexts’) in the human Caco-2 cell line, each exposed to 11 different culture media (‘culture contexts’) that mimic conditions relevant in the colon and colorectal cancer. We identified four effectors present in complex with KRAS in all genetic and growth contexts (‘context-general effectors’). Seven effectors are found in KRAS complexes in only some contexts (‘context-specific effectors’). Analyzing all interactors in complex with KRAS per condition, we find that the culture contexts had a larger impact on interaction rewiring than genetic contexts. We analyzed how changes in the interactome impact functional outcomes and created interactive shiny app for interactive visualization. We validated some of the functional differences in metabolism and proliferation. Finally, we used networks to evaluate how KRAS effectors are involved in the modulation of functions by random walk analyses of effector-mediated (sub)complexes. Altogether, our work shows the impact of environmental contexts on network rewiring, which provides insides into tissue-specific signaling mechanisms. This may also explain why KRAS oncogenic mutants may be causing cancer only in specific tissues despite KRAS being expressed in most cells and tissues.
HostingRepositoryPRIDE
AnnounceDate2023-02-23
AnnouncementXMLSubmission_2023-02-23_07:40:38.251.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterKieranWynne
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumenttimsTOF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-07-20 00:12:16ID requested
12023-02-23 07:40:38announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: KRAS, affinity purification (AP)-mass spectrometry (MS), protein-protein interactions
Contact List
ChristinaKiel
contact affiliationAssociate Professor of Systems Biology Department of Molecular Medicine University of Pavia 9, via A Ferrata/ 27100 Pavia / Italy
contact emailchristina.kiel@unipv.it
lab head
KieranWynne
contact affiliationUniversity College Dublin
contact emailkieran.wynne1@ucd.ie
dataset submitter
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Dataset FTP location
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