ArticleScience advances2023
Molecular evolution of Keap1 was essential for adaptation of vertebrates to terrestrial life.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 19 citations in OpenAlex.
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- ROS produced by Dual oxidase regulate cell proliferation and haemocyte migration during leg regeneration in the cricket.Development (Cambridge, England) · 2025Article
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- Running a genetic stop sign accelerates oxygen metabolism and energy production in horses.Science (New York, N.Y.) · 2025Article
- Model organisms for investigating the functional involvement of NRF2 in non-communicable diseases.Redox biology · 2025Review
- Immune Cell Profiling Reveals a Common Pattern in Premetastatic Niche Formation Across Various Cancer Types.Cancer medicine · 2025Article
- Promising tools into oxidative stress: A review of non-rodent model organisms.Redox biology · 2024Review
- The hydrophobicity of the CARD8 N-terminus tunes inflammasome activation.Cell chemical biology · 2024Article
- CRL2Oncogene · 2024Article
- Reactive Oxygen Species Signaling and Oxidative Stress: Transcriptional Regulation and Evolution.Antioxidants (Basel, Switzerland) · 2024Review
- Understanding mechanisms of antioxidant action in health and disease.Nature reviews. Molecular cell biology · 2024Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reactive oxygen species (ROS) posed a risk for the transition of vertebrates from aquatic to terrestrial life. How ancestral organisms adapted to such ROS exposure has remained a mystery. Here, we show that attenuation of the activity of the ubiquitin ligase CRL3Keap1 for the transcription factor Nrf2 during evolution was key to development of an efficient response to ROS exposure. The Keap1 gene was duplicated in fish to give rise to Keap1A and the only remaining mammalian paralog Keap1B, the latter of which shows a lower affinity for Cul3 and contributes to robust Nrf2 induction in response to ROS exposure. Mutation of mammalian Keap1 to resemble zebrafish Keap1A resulted in an attenuated Nrf2 response, and most knock-in mice expressing such a Keap1 mutant died on exposure as neonates to sunlight-level ultraviolet radiation. Our results suggest that molecular evolution of Keap1 was essential for adaptation to terrestrial life.
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