PXD016431

PXD016431 is an original dataset announced via ProteomeXchange.

Title	Extensive Rewiring of the the Epidermal Growth Factor Receptor EGFR Networks in Colorectal Cancer Cells Expressing Transforming Levels of Oncogenic KRASG13D
Description	Protein-protein-interaction networks (PPINs) organize fundamental biological processes, but how oncogenic mutations impact these interactions and their functions at a network-level scale is poorly understood. Here, we analyze how a common oncogenic KRAS mutation (KRASG13D) affects PPIN structure and function of the Epidermal Growth Factor Receptor (EGFR) network in colorectal cancer (CRC) cells. Mapping >6,000 PPIs shows that this network is extensively rewired in cells expressing transforming levels of KRASG13D (mtKRAS). The factors driving PPIN rewiring are multifactorial including changes in protein expression and phosphorylation. Mathematical modelling also suggests that the binding dynamics of low and high affinity KRAS interactors contribute to rewiring. PPIN rewiring substantially alters the composition of protein complexes, signal flow, transcriptional regulation, and cellular phenotype. These changes are validated by targeted and global experimental analysis. Importantly, genetic alterations in the most extensively rewired PPIN nodes occur frequently in CRC and are prognostic of poor patient outcomes.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:59:13.627.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mohamed Ali Jarboui
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-11-25 05:11:40	ID requested
1	2019-12-04 01:15:07	announced
2	2020-02-17 01:44:07	announced	2020-02-17: Updated publication reference for PubMed record(s): 31980649.
⏵ 3	2024-10-22 04:59:21	announced	2024-10-22: Updated project metadata.

10.1038/s41467-019-14224-9;

Kennedy SA, Jarboui MA, Srihari S, Raso C, Bryan K, Dernayka L, Charitou T, Bernal-Llinares M, Herrera-Montavez C, Krstic A, Matallanas D, Kotlyar M, Jurisica I, Curak J, Wong V, Stagljar I, LeBihan T, Imrie L, Pillai P, Lynn MA, Fasterius E, Al-Khalili Szigyarto C, Breen J, Kiel C, Serrano L, Rauch N, Rukhlenko O, Kholodenko BN, Iglesias-Martinez LF, Ryan CJ, Pilkington R, Cammareri P, Sansom O, Shave S, Auer M, Horn N, Klose F, Ueffing M, Boldt K, Lynn DJ, Kolch W, . Nat Commun, 11(1):499(2020) [pubmed]

curator keyword: Biomedical

submitter keyword: Extensive Rewiring of the the Epidermal Growth Factor Receptor EGFR Networks in Colorectal Cancer Cells Expressing Transforming Levels of Oncogenic KRASG13D

Mohamed Ali Jarboui
contact affiliation	Core Facility for Medical Bioanalytics Proteomics Platform Tübingen (PxP) Institute for Ophthalmic Research Eberhard-Karls University of Tuebingen Elfriede-Aulhorn-Str. 7 D-72076 Tuebingen. Germany.
contact email	Mohmed-ali.jarboui@uni-tuebingen.de
lab head
Mohamed Ali Jarboui
contact affiliation	Core Facility Medical Poteomics, University Clinic Tuebingen
contact email	mohamed-ali.jarboui@uni-tuebingen.de
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/2019/12/PXD016431

PRIDE project URI

• PRIDE
  1. PXD016431
     1. Label: PRIDE project
     2. Name: Extensive Rewiring of the the Epidermal Growth Factor Receptor EGFR Networks in Colorectal Cancer Cells Expressing Transforming Levels of Oncogenic KRASG13D