PXD036265

PXD036265 is an original dataset announced via ProteomeXchange.

Title	(Full Proteome) Kinase Suppressor of RAS 1 (KSR1) maintains the transformed phenotype of BRAFV600E mutant human melanoma cells
Description	KSR1 is a scaffolding protein for the RAS-RAF-MEK-ERK pathway, which is one of the most frequently altered pathways in human cancers. Previous results have shown that KSR1 has a critical role in mutant RAS mediated transformation. Here, we examined the role of KSR1 in mutant BRAF transformation. We used CRISPR/Cas9 to knock out KSR1 in a BRAFV600E transformed melanoma cell line. KSR1 loss produced a complex phenotype characterized by impaired proliferation, cell cycle defects, decreased transformation, decreased invasive migration, increased cellular senescence, and increased apoptosis. To decipher this phenotype, we used a combination of proteomic ERK substrate profiling, global protein expression profiling, and biochemical validation assays. The results suggest that KSR1 directs ERK to phosphorylate substrates that have a critical role in ensuring cell survival. The results furtherindicate that KSR1 loss induces the activation of p38 Mitogen-Activated Protein Kinase (MAPK) and subsequent cell cycle aberrations and senescence. In summary, KSR1 function plays a key role in oncogenic BRAF transformation.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:04:45.233.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	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-25 13:14:26	ID requested
1	2023-08-15 09:24:39	announced
⏵ 2	2023-11-14 09:04:53	announced	2023-11-14: Updated project metadata.

Liu Z, Krstic A, Neve A, Casalou C, Rauch N, Wynne K, Cassidy H, McCann A, Kavanagh E, McCann B, Blanco A, Rauch J, Kolch W, Kinase Suppressor of RAS 1 (KSR1) Maintains the Transformed Phenotype of BRAFV600E Mutant Human Melanoma Cells. Int J Mol Sci, 24(14):(2023) [pubmed]

submitter keyword: KSR1, Proteomics.,RAS-RAF-MEK-ERK pathway, Cancer

Walter Kolch
contact affiliation	Director Systems Biology Ireland, School of Medicine, University College Dublin.
contact email	walter.kolch@ucd.ie
lab head
Kieran Wynne
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/2023/08/PXD036265

PRIDE project URI

• PRIDE
  1. PXD036265
     1. Label: PRIDE project
     2. Name: (Full Proteome) Kinase Suppressor of RAS 1 (KSR1) maintains the transformed phenotype of BRAFV600E mutant human melanoma cells