The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.
Nrf2:INrf2 (Keap1) signaling in oxidative stress
Open accessAbstract
Nrf2:INrf2(Keap1) are cellular sensors of chemical and radiation induced oxidative and electrophilic stress. Nrf2 is a nuclear transcription factor that controls the expression and coordinated induction of a battery of defensive genes encoding detoxifying enzymes and antioxidant proteins. This is a mechanism of critical importance for cellular protection and cell survival. Nrf2 is retained in the cytoplasm by an inhibitor INrf2. INrf2 functions as an adapter for Cul3/Rbx1 mediated degradation of Nrf2. In response to oxidative/electrophilic stress, Nrf2 is switched on and then off by distinct early and delayed mechanisms. Oxidative/electrophilic modification of INrf2cysteine151 and/or PKC phosphorylation of Nrf2serine40 results in the escape or release of Nrf2 from INrf2. Nrf2 is stabilized and translocates to the nucleus, forms heterodimers with unknown proteins, and binds antioxidant response element (ARE) that leads to coordinated activation of gene expression. It takes less than fifteen minutes from the time of exposure to switch on nuclear import of Nrf2. This is followed by activation of a delayed mechanism that controls switching off of Nrf2 activation of gene expression. GSK3β phosphorylates Fyn at unknown threonine residue(s) leading to nuclear localization of Fyn. Fyn phosphorylates Nrf2tyrosine568 resulting in nuclear export of Nrf2, binding with INrf2 and degradation of Nrf2. The switching on and off of Nrf2 protect cells against free radical damage, prevents apoptosis and promotes cell survival.
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Self-citationThe Keap1 BTB/POZ dimerization function is required to sequester Nrf2 in cytoplasm
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Metadata
- Authors
- Kaspar, J. W., Niture, S. K., & Jaiswal, A. K.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2009-11
- Volume
- 47
- Issue
- 9
- Pages
- 1304-1309
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2161220011
- Cited by
- 1,648
- References
- 16
- FWCI
- 22.92
- Type
- journal article
- Language
- en
- Open access
- green
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