2013
DOI: 10.1016/j.redox.2012.10.001
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The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer

Abstract: The Keap1-Nrf2 pathway is the major regulator of cytoprotective responses to oxidative and electrophilic stress. Although cell signaling pathways triggered by the transcription factor Nrf2 prevent cancer initiation and progression in normal and premalignant tissues, in fully malignant cells Nrf2 activity provides growth advantage by increasing cancer chemoresistance and enhancing tumor cell growth. In this graphical review, we provide an overview of the Keap1-Nrf2 pathway and its dysregulation in cancer cells.… Show more

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Cited by 1,139 publications
(956 citation statements)
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“…The Nrf2 transcriptional activity proceeds with the aid of other co-transcription factors in complex with the former. The stress conditions lead to the suspension of Keap1-Nrf2 interactions and causes transcription of cytoprotective genes like NQO1, GSTs and GCL, which in turn, scavenges the cellular oxidative stress (Kansanen et al 2013) (Fig. 1).…”
Section: Molecular Mechanism Of the Keap1-nrf2 Pathwaymentioning
confidence: 99%
“…The Nrf2 transcriptional activity proceeds with the aid of other co-transcription factors in complex with the former. The stress conditions lead to the suspension of Keap1-Nrf2 interactions and causes transcription of cytoprotective genes like NQO1, GSTs and GCL, which in turn, scavenges the cellular oxidative stress (Kansanen et al 2013) (Fig. 1).…”
Section: Molecular Mechanism Of the Keap1-nrf2 Pathwaymentioning
confidence: 99%
“…The KEAP1/NRF2 pathway is a key pathway for sensing and responding to oxidative stress (Kansanen et al ., 2013). To sustain Nrf2 at the nucleus, GSK3β inhibition by Akt‐mediated phosphorylation at Ser9 is required (Leinonen et al ., 2014).…”
Section: Resultsmentioning
confidence: 99%
“…In response to endogenous and exogenous stresses caused by ROS and electrophiles, NRF2 translocates from the cytoplasm into the nucleus and binds together with small Maf proteins to the Antioxidant Response Element in the regulatory regions of target genes and transactivates expression of genes with antioxidant activity [50]. Small Maf (MafG, MafK and MafF) proteins are b-Zip proteins that lack a transcriptional activation domain.…”
Section: The Transcription Factor Nrf2mentioning
confidence: 99%