PUBLICATION
Identification of the interactive interface and phylogenic conservation of the Nrf2-Keap1 system
- Authors
- Kobayashi, M., Itoh, K., Suzuki, T., Osanai, H., Nishikawa, K., Katoh, Y., Takagi, Y., and Yamamoto, M.
- ID
- ZDB-PUB-020820-4
- Date
- 2002
- Source
- Genes to cells : devoted to molecular & cellular mechanisms 7(8): 807-820 (Journal)
- Registered Authors
- Kobayashi, Makoto, Nakajima-Takagi, Yaeko, Nishikawa, Keizo, Osanai, Hitoshi, Suzuki, Takafumi, Yamamoto, Masayuki
- Keywords
- none
- MeSH Terms
-
- 3T3 Cells
- Adaptor Proteins, Signal Transducing*
- Amino Acid Sequence
- Animals
- Base Sequence
- Binding Sites
- Carrier Proteins/chemistry
- Carrier Proteins/genetics*
- Carrier Proteins/physiology
- Cytoskeletal Proteins*
- DNA Primers
- DNA, Complementary
- DNA-Binding Proteins/chemistry
- DNA-Binding Proteins/genetics*
- DNA-Binding Proteins/physiology
- Hydroquinones/pharmacology
- Mice
- Molecular Sequence Data
- NF-E2-Related Factor 2
- Phylogeny*
- Sequence Homology, Amino Acid
- Trans-Activators/chemistry
- Trans-Activators/genetics*
- Trans-Activators/physiology
- Zebrafish
- Zebrafish Proteins
- PubMed
- 12167159 Full text @ Genes Cells
Citation
Kobayashi, M., Itoh, K., Suzuki, T., Osanai, H., Nishikawa, K., Katoh, Y., Takagi, Y., and Yamamoto, M. (2002) Identification of the interactive interface and phylogenic conservation of the Nrf2-Keap1 system. Genes to cells : devoted to molecular & cellular mechanisms. 7(8):807-820.
Abstract
BACKGROUND: The transcription factor Nrf2 and its negative regulator Keap1 play important roles in transcriptional induction of a set of detoxifying and anti-oxidant enzymes. To gain an insight into our present enigma as to how cells receive oxidative and electrophilic signals and transduce them to Nrf2, we have developed a zebrafish model system for molecular toxicological studies. RESULTS: We systematically cloned zebrafish cytoprotective enzyme cDNAs and found their expression to be efficiently induced by electrophilic agents. We consequently identified the presence of Nrf2 and Keap1 in zebrafish. Both loss- and gain-of-function analyses demonstrated that Nrf2 is the primary regulator of a subset of cytoprotective enzyme genes, while Keap1 suppresses Nrf2 activity in zebrafish. An ETGE motif, critical for the Nrf2-Keap1 interaction, was identified in the Neh2 domain of Nrf2 by reverse two-hybrid screening and found to be indispensable for the regulation of Nrf2 activity in zebrafish.
CONCLUSION: Taken together, these results indicate that the Nrf2-Keap1 system is highly conserved among vertebrates and that the interface between Nrf2 and Keap1 forms an important molecular basis of this regulatory system.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping