Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation

By N. Wakabayashi, K. Itoh, Junko Wakabayashi, Hozumi Motohashi, Shuhei Noda, Satoru Takahashi, S. Imakado, Tomoe Kotsuji, F. Otsuka, D. Roop and 3 more. Nature Genetics, 2003

879 citations recorded by the source corpus.

Subfields: Health, Toxicology and Mutagenesis, Molecular Biology, Pediatrics, Perinatology and Child Health

View Paper: https://www.semanticscholar.org/paper/110cb28d3541f33c513daeca655afec4dda791f8

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Health, Toxicology and Mutagenesis

In Molecular Biology

In Pediatrics, Perinatology and Child Health

Q. Ma

Citations in the corpus

ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis (2007, background): “99) . modification of these Cys residues and possibly others by alkylation , oxidation or disulphide bond formation 100 might displace zinc, thus switching KeaP1 to a conformation that is non-permissive for ubiquitylation.”
Nrf2 redirects glucose and glutamine into anabolic pathways in metabolic reprogramming. (2012, methodology): “These results are consistent with those of our previous reports (Wakabayashi et al., 2003; Taguchi et al., 2010).”
Role of nrf2 in oxidative stress and toxicity. (2013, background): “Knockout of Keap1 in mice resulted in constitutive activation of Nrf2 from stabilization of Nrf2 protein (44).”
Molecular Mechanisms of Nrf2-Mediated Antioxidant Response (2009, background): “Gene knockout of Keap1 resulted in constitutively hyperactive Nrf2 signaling [26-28].”
Antioxidant responses and cellular adjustments to oxidative stress (2015, background): “Interestingly, Keap1 knockout mice die short after birth, but the lethal phenotype can be reversed by the double knockout of Keap1 and Nrf2 [64], which suggests that either excessive or insufficient Nrf2 activity may be detrimental for normal physiology.”
Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis (2010, methodology): “Disruption of Keap1 (Keap1 / ) leads to enhanced nuclear accumulation of Nrf2 and elevated expression of Nrf2-regulated genes (33).”
The Impact of Oxidative Stress and Inflammation on RPE Degeneration in Non-neovascular AMD (2017, background): “The released Nrf2 then translocates to the nucleus, where it dimerizes with Maf proteins, and binds to the antioxidant response element (ARE) in the promoters of its target genes to initiate transcription (Dinkova-Kostova et al., 2005; Kobayashi and Yamamoto, 2005; Wakabayashi et al., 2003).”
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis (2011, neutral): “(3) 5′-CAUGUUACGUGAUGAGGAU-3′ (4) 5′-GGACAGCAAUUACCAUUUU-3′”
An Integrated Metabolic Atlas of Clear Cell Renal Cell Carcinoma (2016, neutral): “Mutations in the KEAP1/NRF2 axis have been shown to promote tumor invasiveness and resistance to oxidative stress in pancreatic cancers (DeNicola et al., 2011).”