Abstract
Transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2) controls cellular adaptation to oxidants and electrophiles by inducing antioxidant and detoxification genes in response to redox stress. NRF2 is negatively regulated by Kelch-like ECH-associated protein 1 (KEAP1). Tumours from similar to 15% of patients with lung cancer harbour somatic mutations in KEAP1 that prevent effective NRF2 repression. Recently, two NRF2 mutation 'hot-spots' were identified in similar to 10% of patients with lung cancer, enabling the transcription factor to evade KEAP1-mediated repression. Somatic mutations in KEAP1 and NRF2 provide an insight into the molecular mechanisms by which NRF2 is regulated. Moreover, constitutive NRF2 activation might cause drug resistance in tumours, and an understanding of how the transcription factor is regulated indicates ways in which this could be overcome.
Original language | English |
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Pages (from-to) | 176-188 |
Number of pages | 13 |
Journal | Trends in Biochemical Sciences |
Volume | 34 |
Issue number | 4 |
DOIs | |
Publication status | Published - Apr 2009 |
Keywords
- TRANSCRIPTION FACTOR NRF2
- GLUTATHIONE S-TRANSFERASES
- CHEMOPREVENTIVE AGENT SULFORAPHANE
- DRUG-METABOLIZING-ENZYMES
- UBIQUITIN LIGASE COMPLEX
- CUL3-BASED E3 LIGASE
- ANTIOXIDANT RESPONSE
- OXIDATIVE STRESS
- GENE-EXPRESSION
- LUNG-CANCER