PXD035399-1

PXD035399 is an original dataset announced via ProteomeXchange.

Title	Analysis of context-specific KRAS-effectors (sub)complexes in Caco-2 cells
Description	Ras 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.
HostingRepository	PRIDE
AnnounceDate	2023-02-23
AnnouncementXML	Submission_2023-02-23_07:40:38.251.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	KieranWynne
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF

Revision	Datetime	Status	ChangeLog Entry
0	2022-07-20 00:12:16	ID requested
⏵ 1	2023-02-23 07:40:38	announced

Dataset with its publication pending

submitter keyword: KRAS, affinity purification (AP)-mass spectrometry (MS), protein-protein interactions

ChristinaKiel
contact affiliation	Associate Professor of Systems Biology Department of Molecular Medicine University of Pavia 9, via A Ferrata/ 27100 Pavia / Italy
contact email	christina.kiel@unipv.it
lab head
KieranWynne
contact affiliation	University College Dublin
contact email	kieran.wynne1@ucd.ie
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/2023/02/PXD035399

PRIDE project URI

• PRIDE
  1. PXD035399
     1. Label: PRIDE project
     2. Name: Analysis of context-specific KRAS-effectors (sub)complexes in Caco-2 cells