PXD036261-1

PXD036261 is an original dataset announced via ProteomeXchange.

Title	(AP-MS) 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 further indicate 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	2023-10-24
AnnouncementXML	Submission_2023-10-24_11:30:46.718.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
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-25 13:05:12	ID requested
⏵ 1	2023-10-24 11:30:47	announced
2	2023-11-14 09:07:52	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,RAS_RAF-MEK-ERK pathway, melanoma, apoptosis, proliferation, senescence

WalterKolch
contact affiliation	Systems Biology Ireland, School of Medicine, University College Dublin, Dublin 4, Ireland
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. PXD036261
     1. Label: PRIDE project
     2. Name: (AP-MS) Kinase Suppressor of RAS 1 (KSR1) maintains the transformed phenotype of BRAFV600E mutant human melanoma cells