The DOI matches its Crossref record; 17 of the 17 references it cites were found in a registry or an index.
Molecular mechanisms of Nrf2‐mediated antioxidant response
Open accessAbstract
Nrf2 is the key transcription factor regulating the antioxidant response. Nrf2 signaling is repressed by Keap1 at basal condition and induced by oxidative stress. Keap1 is recently identified as a Cullin 3‐dependent substrate adaptor protein. A two‐sites binding “hinge & latch” model vividly depicts how Keap1 can efficiently present Nrf2 as substrate for ubiquitination. Oxidative perturbation can impede Keap1‐mediated Nrf2 ubiquitination but fail to disrupt Nrf2/Keap1 binding. Nrf2 per se is a redox‐sensitive transcription factor. A new Nrf2‐mediated redox signaling model is proposed based on these new discoveries. Free floating Nrf2 protein functions as a redox‐sensitive probe. Keap1 instead functions as a gate keeper to control the availability of Nrf2 probes and thus regulates the overall sensitivity of the redox signaling. © 2008 Wiley‐Liss, Inc.
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Function and regulation of cullin–RING ubiquitin ligases
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Nrf2–Keap1 defines a physiologically important stress response mechanism
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“domain, enabling Nrf2 to form heterodimer with the ZIP domain of small Maf proteins [1].”
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“Nrf2 is a short-live protein, rapidly degraded in a ubiquitin-dependent manner [23,34,58].”
Wakabayashi, N., Dinkova-Kostova, A. T., Holtzclaw, W. D., Kang, M.-I., Kobayashi, A., Yamamoto, M., Kensler, T. W., & Talalay, P. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307301101 · Cited by 986 · cited 9×
“substantially high amount of Nrf2/Keap1 dimers remained undisrupted in SFN and tBHQ induced antioxidant response [26,34,49,56,57].”
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“It is very interesting to observe that in this nine-turns a-helix, six of seven lysine residues are located on the same side [55].”
BackgroundInfluential
Cited by
Modulation of oxidative stress as an anticancer strategy
Gorrini, C., Harris, I. S., & Mak, T. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd4002 · Cited by 3,579
Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions
Lushchak, V. I. (2012) · Journal of Amino Acids · doi:10.1155/2012/736837 · Cited by 1,266
Stress-activated cap’n’collar transcription factors in aging and human disease
Sykiotis, G. P., & Bohmann, D. (2010) · Science Signaling · doi:10.1126/scisignal.3112re3 · Cited by 776
Small Molecule Modulators of Keap1‐ Nrf2‐ ARE Pathway as Potential Preventive and Therapeutic Agents
Magesh, S., Chen, Y., & Hu, L. (2012) · Medicinal Research Reviews · doi:10.1002/med.21257 · Cited by 760
“146 Recently, the fluorescein-based biarsenical thiol labeling reagent (FlAsH-EDT2, 74) and phenylarsine oxide (75) were found to produce Keap1-dependent activation of Nrf2.”
BackgroundPollier, J., & Goossens, A. (2012) · Phytochemistry · doi:10.1016/j.phytochem.2011.12.022 · Cited by 499
Metadata
- Authors
- Li, W., & Kong, A.
- Venue
- Molecular Carcinogenesis
- Publisher
- Wiley
- Published
- 2008-07-10
- Volume
- 48
- Issue
- 2
- Pages
- 91-104
- ISSN
- 0899-1987 (ISSN-L)
- 1098-2744
- OpenAlex
- W2096000363
- Cited by
- 785
- References
- 17
- FWCI
- 15.14
- Type
- journal article
- Language
- en
- Open access
- green
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