All

What are you looking for?

All
Projects
Results
Organizations

Quick search

  • Projects supported by TA ČR
  • Excellent projects
  • Projects with the highest public support
  • Current projects

Smart search

  • That is how I find a specific +word
  • That is how I leave the -word out of the results
  • “That is how I can find the whole phrase”

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%2F68081707%3A_____%2F18%3A00488412" target="_blank" >RIV/68081707:_____/18:00488412 - isvavai.cz</a>

  • Alternative codes found

    RIV/00216224:14110/18:00100832 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

  • Czech description

Classification

  • Type

    J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database

  • CEP classification

  • 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

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

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

  • 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