Kinase Suppressor of RAS 1 (KSR1) Maintains the Transformed Phenotype of BRAFV600E Mutant Human Melanoma Cells
Overview
Chemistry
Molecular Biology
Authors
Affiliations
Kinase Suppressor of RAS 1 (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 characterised 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.
Liu B, Chen M, Liang Y, Mei Z, Sun W, Gao W Hum Cell. 2024; 38(1):23.
PMID: 39614918 DOI: 10.1007/s13577-024-01155-x.
Imaging the Raf-MEK-ERK Signaling Cascade in Living Cells.
Shin Y, Cho M, Hwang J, Myung K, Kweon H, Lee Z Int J Mol Sci. 2024; 25(19).
PMID: 39408915 PMC: 11477372. DOI: 10.3390/ijms251910587.
Enzyme Is the Name-Adapter Is the Game.
Huber M, Brummer T Cells. 2024; 13(15.
PMID: 39120280 PMC: 11311582. DOI: 10.3390/cells13151249.