Metabolic stress regulates ERK activity by controlling KSR-RAF heterodimerization
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14110%2F18%3A00100832" target="_blank" >RIV/00216224:14110/18:00100832 - isvavai.cz</a>
Alternative codes found
RIV/68081707:_____/18:00488412 RIV/00159816:_____/18:00068618 RIV/00216208:11120/18:43916007
Result on the web
<a href="http://dx.doi.org/10.15252/embr.201744524" target="_blank" >http://dx.doi.org/10.15252/embr.201744524</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.15252/embr.201744524" target="_blank" >10.15252/embr.201744524</a>
Alternative languages
Result language
angličtina
Original language name
Metabolic stress regulates ERK activity by controlling KSR-RAF heterodimerization
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
EMBO reports
ISSN
1469-221X
e-ISSN
1469-3178
Volume of the periodical
19
Issue of the periodical within the volume
2
Country of publishing house
US - UNITED STATES
Number of pages
17
Pages from-to
320-336
UT code for WoS article
000424166400015
EID of the result in the Scopus database
2-s2.0-85038839357