We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation.
- Authors
Wakabayashi, Nobunao; Itoh, Ken; Wakabayashi, Junko; Motohashi, Hozumi; Noda, Shuhei; Takahashi, Satoru; Imakado, Sumihisa; Kotsuji, Tomoe; Otsuka, Fujio; Roop, Dennis R; Harada, Takanori; Engel, James Douglas; Yamamoto, Masayuki
- Abstract
Transcription factor Nrf2 (encoded by Nfe2l2) regulates a battery of detoxifying and antioxidant genes, and Keap1 represses Nrf2 function. When we ablated Keap1, Keap1-deficient mice died postnatally, probably from malnutrition resulting from hyperkeratosis in the esophagus and forestomach. Nrf2 activity affects the expression levels of several squamous epithelial genes. Biochemical data show that, without Keap1, Nrf2 constitutively accumulates in the nucleus to stimulate transcription of cytoprotective genes. Breeding to Nrf2-deficient mice reversed the phenotypic Keap1 deficiencies. These experiments show that Keap1 acts upstream of Nrf2 in the cellular response to oxidative and xenobiotic stress.
- Publication
Nature genetics, 2003, Vol 35, Issue 3, p238
- ISSN
1061-4036
- Publication type
Journal Article
- DOI
10.1038/ng1248