دورية أكاديمية
The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation.
| العنوان: | The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. |
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| المؤلفون: | Bryan HK; MRC Centre for Drug Safety Science, Molecular & Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, L69 3GE, UK., Olayanju A, Goldring CE, Park BK |
| المصدر: | Biochemical pharmacology [Biochem Pharmacol] 2013 Mar 15; Vol. 85 (6), pp. 705-17. Date of Electronic Publication: 2012 Dec 05. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't; Review |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Country of Publication: England NLM ID: 0101032 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-2968 (Electronic) Linking ISSN: 00062952 NLM ISO Abbreviation: Biochem Pharmacol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Oxford : Elsevier Science Original Publication: Oxford, New York [etc.] Paragamon Press. |
| مواضيع طبية MeSH: | Intracellular Signaling Peptides and Proteins/*physiology , NF-E2-Related Factor 2/*physiology, Animals ; Humans ; Kelch-Like ECH-Associated Protein 1 |
| مستخلص: | The transcription factor Nrf2 (NF-E2-related factor 2) plays a vital role in maintaining cellular homeostasis, especially upon the exposure of cells to chemical or oxidative stress, through its ability to regulate the basal and inducible expression of a multitude of antioxidant proteins, detoxification enzymes and xenobiotic transporters. In addition, Nrf2 contributes to diverse cellular functions including differentiation, proliferation, inflammation and lipid synthesis and there is an increasing association of aberrant expression and/or function of Nrf2 with pathologies including cancer, neurodegeneration and cardiovascular disease. The activity of Nrf2 is primarily regulated via its interaction with Keap1 (Kelch-like ECH-associated protein 1), which directs the transcription factor for proteasomal degradation. Although it is generally accepted that modification (e.g. chemical adduction, oxidation, nitrosylation or glutathionylation) of one or more critical cysteine residues in Keap1 represents a likely chemico-biological trigger for the activation of Nrf2, unequivocal evidence for such a phenomenon remains elusive. An increasing body of literature has revealed alternative mechanisms of Nrf2 regulation, including phosphorylation of Nrf2 by various protein kinases (PKC, PI3K/Akt, GSK-3β, JNK), interaction with other protein partners (p21, caveolin-1) and epigenetic factors (micro-RNAs -144, -28 and -200a, and promoter methylation). These and other processes are potentially important determinants of Nrf2 activity, and therefore may contribute to the maintenance of cellular homeostasis. Here, we dissect evidence supporting these Keap1-dependent and -independent mechanisms of Nrf2 regulation. Furthermore, we highlight key knowledge gaps in this important field of biology, and suggest how these may be addressed experimentally. (Copyright © 2012 Elsevier Inc. All rights reserved.) |
| معلومات مُعتمدة: | United Kingdom Medical Research Council |
| المشرفين على المادة: | 0 (Intracellular Signaling Peptides and Proteins) 0 (KEAP1 protein, human) 0 (Kelch-Like ECH-Associated Protein 1) 0 (NF-E2-Related Factor 2) 0 (NFE2L2 protein, human) |
| تواريخ الأحداث: | Date Created: 20121211 Date Completed: 20130419 Latest Revision: 20220317 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1016/j.bcp.2012.11.016 |
| PMID: | 23219527 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-2968 |
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| DOI: | 10.1016/j.bcp.2012.11.016 |