Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy

By T. Shibata, T. Ohta, K. I. Tong, A. Kokubu, Reiko Odogawa, K. Tsuta, H. Asamura, Masayuki Yamamoto, S. Hirohashi. Proceedings of the National Academy of Sciences of the United States of America, 2008

761 citations recorded by the source corpus.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d4ad8d93fedd08696f2015fd5b6e645e97a4320d

How researchers see this paper

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

In Molecular Biology

Citations in the corpus

The Dual Roles of NRF2 in Cancer. (2016, background): “In addition,NRF2 mutations have been found in human head and neck cancer [48], larynx, esophagus, and skin SCC [50], and all of them cluster near or within the Neh2 domain48 and 50.”
Nrf2:INrf2(Keap1) Signaling in Oxidative Stress (2009, background): “A recent study reported that somatic mutations also occur in the coding region of Nrf2, especially in cancer patients with a history of smoking or suffering from squamous cell carcinoma [101].”
Brusatol enhances the efficacy of chemotherapy by inhibiting the Nrf2-mediated defense mechanism (2011, background): “Moreover, no mutation was found in either Nrf2 or Keap1 in HeLa cells (7, 25).”
Regulation of Nrf2 – An update (2013, background): “Mutations are also known in the region of Nrf2 that interacts with INrf2 leading to stabilization of Nrf2, nuclear accumulation of Nrf2, activation of cytoprotective proteins, reduced apoptosis and increased cell survival [86].”
The Roles of NRF2 in Modulating Cellular Iron Homeostasis (2017, background): “For example, somatic mutations that activate NRF2 or inhibit KEAP1-mediated degradation of NRF2 have shown prevalence in many cancers (40, 138).”
Autophagy-deficient mice develop multiple liver tumors. (2011, result): “7) can be important for progression of tumors and is consistent with reports that somatic mutations in either Keap1 or Nrf2 that cause constitutive Nrf2 activation have been found in human cancers (Padmanabhan et al. 2006; Shibata et al. 2008).”
Lessons from the cancer genome. (2013, neutral): “And, a pathway that governs the oxidative stress response in all cells (the KEAP1/ NRF2-signaling pathway) is activated by mutation in >30% of squamous lung cancers (Hammerman et al., 2012; Shibata et al., 2008).”
Role of Glutathione in Cancer Progression and Chemoresistance (2013, background): “Moreover, it has been observed that the prognosis of patients with either Nrf2 or Keap1 mutations is much lower than patients with no mutation [83].”
Persistent activation of Nrf2 through p62 in hepatocellular carcinoma cells (2011, background): “…to constitutive activation of Nrf2, followed by induction of Nrf2 target genes, such as cytoprotective enzymes, antioxidant proteins, and multi-drug efflux pumps, thus conferring resistance of tumor cells to oxidative stress and anticancer agents (Shibata et al., 2008b; Hayes and McMahon, 2009).”
Nrf2 is controlled by two distinct β-TrCP recognition motifs in its Neh6 domain, one of which can be modulated by GSK-3 activity. (2012, background): “Alternatively, Nrf2 may evade repression by Keap1 as a consequence of somatic mutations in the ETGE and DLG motifs of the CNC-bZIP factor, or by overexpression of the Nrf2 gene (21-23).”