Molecular cross-talk between the NRF2/KEAP1 signaling pathway, autophagy, and apoptosis.
| Title: | Molecular cross-talk between the NRF2/KEAP1 signaling pathway, autophagy, and apoptosis. |
|---|---|
| Authors: | Stępkowski TM; Institute of Nuclear Chemistry and Technology, Center for Radiobiology and Biological Dosimetry, 03-195 Warsaw, Poland. t.stepkowski@ichtj.waw.pl; Kruszewski MK |
| Source: | Free radical biology & medicine [Free Radic Biol Med] 2011 May 01; Vol. 50 (9), pp. 1186-95. Date of Electronic Publication: 2011 Feb 02. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 8709159 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4596 (Electronic) Linking ISSN: 08915849 NLM ISO Abbreviation: Free Radic Biol Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: Tarrytown, NY : Elsevier Science; Original Publication: New York : Pergamon, c1987- |
| MeSH Terms: | Apoptosis* ; Autophagy* ; Oxidative Stress*; Signal Transduction/*physiology ; Sulfhydryl Compounds/*metabolism; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Antigens, Nuclear/genetics ; Antigens, Nuclear/metabolism ; Carrier Proteins/genetics ; Carrier Proteins/metabolism ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Cell Transformation, Neoplastic/pathology ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; MAP Kinase Kinase Kinase 5/genetics ; MAP Kinase Kinase Kinase 5/metabolism ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/metabolism ; NF-E2-Related Factor 2/genetics ; NF-E2-Related Factor 2/metabolism ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/metabolism ; Neurodegenerative Diseases/pathology ; Protein Precursors/genetics ; Protein Precursors/metabolism ; Reactive Oxygen Species/metabolism ; Thymosin/analogs & derivatives ; Thymosin/genetics ; Thymosin/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Amino Acid Motifs ; Animals ; Gene Expression Regulation ; Humans ; Kelch-Like ECH-Associated Protein 1 ; Oxidation-Reduction ; Phosphoprotein Phosphatases ; Phosphorylation ; Protein Binding ; Sequestosome-1 Protein ; Ubiquitination ; Bromodomain Containing Proteins |
| Abstract: | Oxidative stress, perturbations in the cellular thiol level and redox balance, affects many cellular functions, including signaling pathways. This, in turn, may cause the induction of autophagy or apoptosis. The NRF2/KEAP1 signaling pathway is the main pathway responsible for cell defense against oxidative stress and maintaining the cellular redox balance at physiological levels. The relation between NRF2/KEAP1 signaling and regulation of apoptosis and autophagy is not well understood. In this hypothesis article we discuss how KEAP1 protein and its direct interactants (such as PGAM5, prothymosin α, FAC1 (BPTF), and p62) provide a molecular foundation for a possible cross-talk between NRF2/KEAP1, apoptosis, and autophagy pathways. We present a hypothesis for how NRF2/KEAP1 may interfere with the cellular apoptosis-regulatory machinery through activation of the ASK1 kinase by a KEAP1 binding partner-PGAM5. Based on very recent experimental evidence, new hypotheses for a cross-talk between NF-κB and the NRF2/KEAP1 pathway in the context of autophagy-related "molecular hub" protein p62 are also presented. The roles of KEAP1 molecular binding partners in apoptosis regulation during carcinogenesis and in neurodegenerative diseases are also discussed.; (Copyright © 2011 Elsevier Inc. All rights reserved.) |
| Substance Nomenclature: | 0 (Adaptor Proteins, Signal Transducing); 0 (Antigens, Nuclear); 0 (Carrier Proteins); 0 (Intracellular Signaling Peptides and Proteins); 0 (Kelch-Like ECH-Associated Protein 1); EC 2.7.11.25 (MAP Kinase Kinase Kinase 5); 0 (Mitochondrial Proteins); 0 (NF-E2-Related Factor 2); 0 (NF-kappa B); 0 (Nerve Tissue Proteins); EC 3.1.3.16 (Phosphoprotein Phosphatases); 0 (Protein Precursors); 0 (Reactive Oxygen Species); 0 (Sequestosome-1 Protein); 0 (Sulfhydryl Compounds); 61512-21-8 (Thymosin); 0 (Transcription Factors); 0 (KEAP1 protein, human); 0 (SQSTM1 protein, human); 0 (fetal Alzheimer antigen); 0 (Bromodomain Containing Proteins); 0 (prothymosin alpha); EC 3.1.3.16 (PGAM5 protein, human) |
| Entry Date(s): | Date Created: 20110208 Date Completed: 20110808 Latest Revision: 20260128 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.freeradbiomed.2011.01.033 |
| PMID: | 21295136 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't