PXD036792-1

PXD036792 is an original dataset announced via ProteomeXchange.

Title	Interactome dynamics of RAF1-BRAF kinase monomers and dimers
Description	RAF kinases play major roles in cancer. BRAFV600E mutants drive ~6% of human cancers. Potent kinase inhibitors exist but show variable effects in different cancer types, sometimes even inducing paradoxical RAF kinase activation. Both paradoxical activation and drug resistance are frequently due to enhanced dimerization between RAF1 and BRAF, which maintains or restores the activity of the downstream MEK-ERK pathway. Here, using quantitative proteomics we mapped the interactomes of RAF1 monomers, RAF1-BRAF and RAF1-BRAFV600E dimers identifying and quantifying >1,000 proteins. In addition, we examined the effects of vemurafenib and sorafenib, two different types of clinically used RAF inhibitors. Using regression analysis to compare different conditions we found a large overlapping core interactome but also distinct condition specific differences. Given that RAF proteins have kinase independent functions such dynamic interactome changes could contribute to their functional diversification. Analysing this dataset may provide a deeper understanding of RAF signalling and mechanisms of resistance to RAF inhibitors.
HostingRepository	PRIDE
AnnounceDate	2023-02-27
AnnouncementXML	Submission_2023-02-27_12:27:36.668.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	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-17 02:53:33	ID requested
⏵ 1	2023-02-27 12:27:37	announced
2	2023-11-14 07:39:37	announced	2023-11-14: Updated project metadata.

submitter keyword: RAF1, BRAF, dimerization,RAF kinase, interactome

WalterKolch
contact affiliation	Systems Biology Ireland, University College Dublin
contact email	walter.kolch@ucd.ie
lab head
KieranWynne
contact affiliation	University College Dublin
contact email	kieran.wynne1@ucd.ie
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036792
     1. Label: PRIDE project
     2. Name: Interactome dynamics of RAF1-BRAF kinase monomers and dimers