Regulation of Nrf2 by phosphorylation: Consequences for biological function and therapeutic implications

The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) participates in the activation of the antioxidant cytoprotective pathway and other important physiological processes to maintain cellular homeostasis. The dysregulation of NRF2 activity plays a role in various diseases, such a...

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Published inFree radical biology & medicine Vol. 168; pp. 129 - 141
Main Authors Liu, Tian, Lv, Yi-Fei, Zhao, Jing-Long, You, Qi-Dong, Jiang, Zheng-Yu
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 20.05.2021
Subjects
Cellular protection
NRF2
Oxidative stress
Phosphorylation
Posttranslational modification
Regulation
Posttranslational modification
Oxidative stress
Phosphorylation
Regulation
Cellular protection
NRF2
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Abstract The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) participates in the activation of the antioxidant cytoprotective pathway and other important physiological processes to maintain cellular homeostasis. The dysregulation of NRF2 activity plays a role in various diseases, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Thus, NRF2 activity is tightly regulated through multiple mechanisms, among which phosphorylation by kinases is critical in the posttranslational regulation of NRF2. For instance, PKC, casein kinase 2, and AMP-activated kinase positively, while GSK-3 negatively regulates NRF2 activity through phosphorylation of different sites. Here, we provide an overview of the phosphorylation regulation pattern of NRF2 and discuss the therapeutic potential of interventions targeting NRF2 phosphorylation. [Display omitted] •Protein kinases phosphorylate Nrf2 to modulate its stability and/or activity.•Phosphorylation regulation of NRF2 bridges NRF2 activity to a series of biological events.•Targeting NRF2 phosphorylation regulation shows therapeutic potential for multiple inflammation-related diseases.
AbstractList The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) participates in the activation of the antioxidant cytoprotective pathway and other important physiological processes to maintain cellular homeostasis. The dysregulation of NRF2 activity plays a role in various diseases, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Thus, NRF2 activity is tightly regulated through multiple mechanisms, among which phosphorylation by kinases is critical in the posttranslational regulation of NRF2. For instance, PKC, casein kinase 2, and AMP-activated kinase positively, while GSK-3 negatively regulates NRF2 activity through phosphorylation of different sites. Here, we provide an overview of the phosphorylation regulation pattern of NRF2 and discuss the therapeutic potential of interventions targeting NRF2 phosphorylation.The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) participates in the activation of the antioxidant cytoprotective pathway and other important physiological processes to maintain cellular homeostasis. The dysregulation of NRF2 activity plays a role in various diseases, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Thus, NRF2 activity is tightly regulated through multiple mechanisms, among which phosphorylation by kinases is critical in the posttranslational regulation of NRF2. For instance, PKC, casein kinase 2, and AMP-activated kinase positively, while GSK-3 negatively regulates NRF2 activity through phosphorylation of different sites. Here, we provide an overview of the phosphorylation regulation pattern of NRF2 and discuss the therapeutic potential of interventions targeting NRF2 phosphorylation.
The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) participates in the activation of the antioxidant cytoprotective pathway and other important physiological processes to maintain cellular homeostasis. The dysregulation of NRF2 activity plays a role in various diseases, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Thus, NRF2 activity is tightly regulated through multiple mechanisms, among which phosphorylation by kinases is critical in the posttranslational regulation of NRF2. For instance, PKC, casein kinase 2, and AMP-activated kinase positively, while GSK-3 negatively regulates NRF2 activity through phosphorylation of different sites. Here, we provide an overview of the phosphorylation regulation pattern of NRF2 and discuss the therapeutic potential of interventions targeting NRF2 phosphorylation. [Display omitted] •Protein kinases phosphorylate Nrf2 to modulate its stability and/or activity.•Phosphorylation regulation of NRF2 bridges NRF2 activity to a series of biological events.•Targeting NRF2 phosphorylation regulation shows therapeutic potential for multiple inflammation-related diseases.
The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) participates in the activation of the antioxidant cytoprotective pathway and other important physiological processes to maintain cellular homeostasis. The dysregulation of NRF2 activity plays a role in various diseases, such as cardiovascular diseases, neurodegenerative diseases, and cancer. Thus, NRF2 activity is tightly regulated through multiple mechanisms, among which phosphorylation by kinases is critical in the posttranslational regulation of NRF2. For instance, PKC, casein kinase 2, and AMP-activated kinase positively, while GSK-3 negatively regulates NRF2 activity through phosphorylation of different sites. Here, we provide an overview of the phosphorylation regulation pattern of NRF2 and discuss the therapeutic potential of interventions targeting NRF2 phosphorylation.
Author Jiang, Zheng-Yu
Zhao, Jing-Long
You, Qi-Dong
Liu, Tian
Lv, Yi-Fei
Author_xml – sequence: 1
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  orcidid: 0000-0003-1546-7490
  surname: Liu
  fullname: Liu, Tian
  organization: State Key Laboratory of Natural Medicines, And Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China
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  orcidid: 0000-0001-9783-6493
  surname: Zhao
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  organization: State Key Laboratory of Natural Medicines, And Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China
– sequence: 4
  givenname: Qi-Dong
  surname: You
  fullname: You, Qi-Dong
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  organization: State Key Laboratory of Natural Medicines, And Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China
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  givenname: Zheng-Yu
  surname: Jiang
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  email: jiangzhengyucpu@163.com
  organization: State Key Laboratory of Natural Medicines, And Jiang Su Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing, 210009, China
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Keywords Posttranslational modification
Oxidative stress
Phosphorylation
Regulation
Cellular protection
NRF2
Language English
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  day: 20
PublicationDecade 2020
PublicationPlace United States
PublicationPlace_xml – name: United States
PublicationTitle Free radical biology & medicine
PublicationTitleAlternate Free Radic Biol Med
PublicationYear 2021
Publisher Elsevier Inc
Publisher_xml – name: Elsevier Inc
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Snippet The transcription factor nuclear factor erythroid-derived 2-like 2 (NRF2) participates in the activation of the antioxidant cytoprotective pathway and other...
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SubjectTerms Cellular protection
NRF2
Oxidative stress
Phosphorylation
Posttranslational modification
Regulation
Title Regulation of Nrf2 by phosphorylation: Consequences for biological function and therapeutic implications
URI https://dx.doi.org/10.1016/j.freeradbiomed.2021.03.034
https://www.ncbi.nlm.nih.gov/pubmed/33794311
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