ArticleLife (Basel, Switzerland)2023
Regulation of Cell Proliferation and Nrf2-Mediated Antioxidant Defense: Conservation of Keap1 Cysteines and Nrf2 Binding Site in the Context of the Evolution of KLHL Family.
Article in Life (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Selenium: From Redox Signaling to Interactions with the Gut Microbiome.Biological trace element research · 2026Review
- Interplay between NRF2 post-translational modifications and protein-protein interactions: Perspectives from emerging structural and functional evidence.Archives of biochemistry and biophysics · 2026Review
- Research Progress on Astaxanthin Plus Exercise for the Prevention and Treatment of Knee Osteoarthritis: A Traditional Narrative Review.International journal of molecular sciences · 2026Review
- Polyphenol-based modulation of the Glo1-Nrf2-RAGE axis in diabetes and neurodegeneration: mechanistic evidence, translational constraints, and critical appraisal.Frontiers in pharmacology · 2026Review
- The Central Role of NRF2 in Cancer Metabolism and Redox Signaling: Novel Insights into Crosstalk with ER Stress and Therapeutic Modulation.Cell biochemistry and biophysics · 2025Review
- The KEAP1-Cullin3-RBX1-Nrf2 Axis in Redox Homeostasis: Molecular Mechanisms, Pathophysiological Roles, and Precision Therapeutic Opportunities.Molecular neurobiology · 2025Review
- Exploring the Interplay of Antioxidants, Inflammation, and Oxidative Stress: Mechanisms, Therapeutic Potential, and Clinical Implications.Diseases (Basel, Switzerland) · 2025Review
- CB5712809, a novel Keap1 inhibitor upregulates SQSTM1/p62 mediated Nrf2 activation to induce cell death in colon cancer cells.Discover oncology · 2025Article
- Review
- Antioxidant-Rich Functional Foods and Exercise: Unlocking Metabolic Health Through Nrf2 and Related Pathways.International journal of molecular sciences · 2025Review
- Glucoraphanin conversion into sulforaphane and related compounds by gut microbiota.Frontiers in physiology · 2025Review
- MicroRNA as Possible Mediators of the Synergistic Effect of Celecoxib and Glucosamine Sulfate in Human Osteoarthritic Chondrocyte Exposed to IL-1β.International journal of molecular sciences · 2023Article
- Intervention of Dietary Protein Levels on Muscle Quality, Antioxidation, and Autophagy in the Muscles of Triploid Crucian Carp (International journal of molecular sciences · 2023Article
- Immunological dimensions of neuroinflammation and microglial activation: exploring innovative immunomodulatory approaches to mitigate neuroinflammatory progression.Frontiers in immunology · 2023Review
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Keap1 (Kelch-like ECH-associated protein 1) is one of the major negative regulators of the transcription factor Nrf2 (nuclear factor erythroid-2-related factor 2), which induces the expression of numerous proteins defending the cell against different stress conditions. Keap1 is generally negatively regulated by post-translational modification (mostly via its cysteine residues) and interaction with other proteins that compete with Nrf2 for binding. Cysteine residues in Keap1 have different effects on protein regulation, as basic residues (Lys, Arg, and His) in close proximity to them increase cysteine modification potential. In this paper, we present an evolutionary analysis of residues involved in both mechanisms of Keap1 regulation in the broader context of the KLHL protein family in vertebrates. We identified the typical domain structure of the KLHL protein family in several proteins outside of this family (namely in KBTBD proteins 2, 3, 4, 6, 7, 8, 12 and 14). We found several cysteines that are flanked by basic residues (namely, C14, C38, C151, C226, C241, C273, C288, C297, C319, and C613) and, therefore, may be considered more susceptible to regulatory modification. The Nrf2 binding site is completely conserved in Keap1 in vertebrates but is absent or located in nonaligned DA and BC loops of the Kelch domain within the KLHL family. The development of specific substrate binding regions could be an evolutionary factor of diversification in the KLHL protein family.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.