2018
Verlande, Amandine; Krafčíková, Michaela; Potěšil, David; Trantírek, Lukáš; Zdráhal, Zbyněk; Elkalaf, Moustafa; Trnka, Jan; Souček, Karel; Rauch, Nora; Rauch, Jens; Kolch, Walter; Uldrijan, Stjepan
Metabolic stress regulates ERK activity by controlling KSR-RAF heterodimerization. Journal Article
In: EMBO reports, vol. 19, no. 2, pp. 320–336, 2018, ISSN: 1469-3178 1469-221X, (Place: England).
Abstract | Links | BibTeX | Tags: *Protein Multimerization, *Stress, 14-3-3 Proteins/chemistry/metabolism, cell cycle arrest, Cell Cycle Checkpoints/genetics, Cell Line, Cell Survival, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases/*metabolism, Glucose/metabolism, Glycolysis, GTP Phosphohydrolases/genetics/metabolism, Humans, Melanoma, Melanoma/genetics/metabolism, Membrane Proteins/genetics/metabolism, metabolic stress, Mutation, Oxygen Consumption, Physiological, Protein Kinases/chemistry/genetics/*metabolism, raf Kinases/chemistry/genetics/*metabolism, RAF‐ERK signaling, Recombinant Fusion Proteins, Tumor
@article{verlande_metabolic_2018,
title = {Metabolic stress regulates ERK activity by controlling KSR-RAF heterodimerization.},
author = {Amandine Verlande and Michaela Krafčíková and David Potěšil and Lukáš Trantírek and Zbyněk Zdráhal and Moustafa Elkalaf and Jan Trnka and Karel Souček and Nora Rauch and Jens Rauch and Walter Kolch and Stjepan Uldrijan},
doi = {10.15252/embr.201744524},
issn = {1469-3178 1469-221X},
year = {2018},
date = {2018-02-01},
journal = {EMBO reports},
volume = {19},
number = {2},
pages = {320–336},
abstract = {Altered cell metabolism is a hallmark of cancer, and targeting specific metabolic nodes is considered an attractive strategy for cancer therapy. In this study, we evaluate the effects of metabolic stressors on the deregulated ERK pathway in melanoma cells bearing activating mutations of the NRAS or BRAF oncogenes. We report that metabolic stressors promote the dimerization of KSR proteins with CRAF in NRAS-mutant cells, and with oncogenic BRAF in BRAF(V600E)-mutant cells, thereby enhancing ERK pathway activation. Despite this similarity, the two genomic subtypes react differently when a higher level of metabolic stress is induced. In NRAS-mutant cells, the ERK pathway is even more stimulated, while it is strongly downregulated in BRAF(V600E)-mutant cells. We demonstrate that this is caused by the dissociation of mutant BRAF from KSR and is mediated by activated AMPK. Both types of ERK regulation nevertheless lead to cell cycle arrest. Besides studying the effects of the metabolic stressors on ERK pathway activity, we also present data suggesting that for efficient therapies of both genomic melanoma subtypes, specific metabolic targeting is necessary.},
note = {Place: England},
keywords = {*Protein Multimerization, *Stress, 14-3-3 Proteins/chemistry/metabolism, cell cycle arrest, Cell Cycle Checkpoints/genetics, Cell Line, Cell Survival, Enzyme Activation, Extracellular Signal-Regulated MAP Kinases/*metabolism, Glucose/metabolism, Glycolysis, GTP Phosphohydrolases/genetics/metabolism, Humans, Melanoma, Melanoma/genetics/metabolism, Membrane Proteins/genetics/metabolism, metabolic stress, Mutation, Oxygen Consumption, Physiological, Protein Kinases/chemistry/genetics/*metabolism, raf Kinases/chemistry/genetics/*metabolism, RAF‐ERK signaling, Recombinant Fusion Proteins, Tumor},
pubstate = {published},
tppubtype = {article}
}