NRF2-regulated cell cycle arrest at early stage of oxidative stress response mechanism

Margita Márton, Nikolett Tihanyi, Pál Gyulavári, G. Bánhegyi, O. Kapuy

Research output: Contribution to journalArticle

Abstract

Oxidative stress results in activation of several signal transduction pathways controlled by the PERK-substrate NRF2 (nuclear factor erythroid 2-related factor 2); meanwhile the ongoing cell division cycle has to be blocked. It has been recently shown that Cyclin D1 got immediately down-regulated via PERK pathway in response to oxidative stress leading to cell cycle arrest. However, the effect of NRF2 on cell cycle regulation has not been explored yet. We aimed to reveal a crosstalk between PERK-substrate NRF2 and the key elements of cell cycle regulatory network upon oxidative stress using molecular biological techniques-Although Cyclin D1 level remained constant, its activity was blocked by various stoichiometric inhibitors (such as p15, p21 and p27) even at low level of oxidative stress. The activity of these CDK inhibitors completely disappeared, when the addition of oxidative agent was combined with silencing of either PERK or NRF2.This further confirms the important role of NRF2 in blocking Cyclin D1 with stoichiometric inhibitors at early stage of oxidative stress.

Original languageEnglish
Article numbere0207949
JournalPLoS One
Volume13
Issue number11
DOIs
Publication statusPublished - Nov 1 2018

Fingerprint

Oxidative stress
Cell Cycle Checkpoints
stress response
Oxidative Stress
oxidative stress
Cells
Cyclin D1
cyclins
Cell Cycle
cell cycle
Signal transduction
Substrates
Crosstalk
signal transduction
cell division
Signal Transduction
Chemical activation
cell cycle checkpoints

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

NRF2-regulated cell cycle arrest at early stage of oxidative stress response mechanism. / Márton, Margita; Tihanyi, Nikolett; Gyulavári, Pál; Bánhegyi, G.; Kapuy, O.

In: PLoS One, Vol. 13, No. 11, e0207949, 01.11.2018.

Research output: Contribution to journalArticle

Márton, Margita ; Tihanyi, Nikolett ; Gyulavári, Pál ; Bánhegyi, G. ; Kapuy, O. / NRF2-regulated cell cycle arrest at early stage of oxidative stress response mechanism. In: PLoS One. 2018 ; Vol. 13, No. 11.
@article{49b63c28fba24907bb9c79c6d71cb4c0,
title = "NRF2-regulated cell cycle arrest at early stage of oxidative stress response mechanism",
abstract = "Oxidative stress results in activation of several signal transduction pathways controlled by the PERK-substrate NRF2 (nuclear factor erythroid 2-related factor 2); meanwhile the ongoing cell division cycle has to be blocked. It has been recently shown that Cyclin D1 got immediately down-regulated via PERK pathway in response to oxidative stress leading to cell cycle arrest. However, the effect of NRF2 on cell cycle regulation has not been explored yet. We aimed to reveal a crosstalk between PERK-substrate NRF2 and the key elements of cell cycle regulatory network upon oxidative stress using molecular biological techniques-Although Cyclin D1 level remained constant, its activity was blocked by various stoichiometric inhibitors (such as p15, p21 and p27) even at low level of oxidative stress. The activity of these CDK inhibitors completely disappeared, when the addition of oxidative agent was combined with silencing of either PERK or NRF2.This further confirms the important role of NRF2 in blocking Cyclin D1 with stoichiometric inhibitors at early stage of oxidative stress.",
author = "Margita M{\'a}rton and Nikolett Tihanyi and P{\'a}l Gyulav{\'a}ri and G. B{\'a}nhegyi and O. Kapuy",
year = "2018",
month = "11",
day = "1",
doi = "10.1371/journal.pone.0207949",
language = "English",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11",

}

TY - JOUR

T1 - NRF2-regulated cell cycle arrest at early stage of oxidative stress response mechanism

AU - Márton, Margita

AU - Tihanyi, Nikolett

AU - Gyulavári, Pál

AU - Bánhegyi, G.

AU - Kapuy, O.

PY - 2018/11/1

Y1 - 2018/11/1

N2 - Oxidative stress results in activation of several signal transduction pathways controlled by the PERK-substrate NRF2 (nuclear factor erythroid 2-related factor 2); meanwhile the ongoing cell division cycle has to be blocked. It has been recently shown that Cyclin D1 got immediately down-regulated via PERK pathway in response to oxidative stress leading to cell cycle arrest. However, the effect of NRF2 on cell cycle regulation has not been explored yet. We aimed to reveal a crosstalk between PERK-substrate NRF2 and the key elements of cell cycle regulatory network upon oxidative stress using molecular biological techniques-Although Cyclin D1 level remained constant, its activity was blocked by various stoichiometric inhibitors (such as p15, p21 and p27) even at low level of oxidative stress. The activity of these CDK inhibitors completely disappeared, when the addition of oxidative agent was combined with silencing of either PERK or NRF2.This further confirms the important role of NRF2 in blocking Cyclin D1 with stoichiometric inhibitors at early stage of oxidative stress.

AB - Oxidative stress results in activation of several signal transduction pathways controlled by the PERK-substrate NRF2 (nuclear factor erythroid 2-related factor 2); meanwhile the ongoing cell division cycle has to be blocked. It has been recently shown that Cyclin D1 got immediately down-regulated via PERK pathway in response to oxidative stress leading to cell cycle arrest. However, the effect of NRF2 on cell cycle regulation has not been explored yet. We aimed to reveal a crosstalk between PERK-substrate NRF2 and the key elements of cell cycle regulatory network upon oxidative stress using molecular biological techniques-Although Cyclin D1 level remained constant, its activity was blocked by various stoichiometric inhibitors (such as p15, p21 and p27) even at low level of oxidative stress. The activity of these CDK inhibitors completely disappeared, when the addition of oxidative agent was combined with silencing of either PERK or NRF2.This further confirms the important role of NRF2 in blocking Cyclin D1 with stoichiometric inhibitors at early stage of oxidative stress.

UR - http://www.scopus.com/inward/record.url?scp=85057567328&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85057567328&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0207949

DO - 10.1371/journal.pone.0207949

M3 - Article

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 11

M1 - e0207949

ER -