The Keap1-Nrf2 system in cancers: Stress response and anabolic metabolism
The Keap1-Nrf2 pathway plays a central role in the protection of cells against oxidative and xenobiotic stresses. Nrf2 is a potent transcription activator that recognizes a unique DNA sequence known as the antioxidant response element (ARE). Under normal conditions, Nrf2 binds to Keap1 in the cyto...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2012-12-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2012.00200/full |
| _version_ | 1811253597740990464 |
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| author | Yoichiro eMitsuishi Hozumi eMotohashi Masayuki eYamamoto |
| author_facet | Yoichiro eMitsuishi Hozumi eMotohashi Masayuki eYamamoto |
| author_sort | Yoichiro eMitsuishi |
| collection | DOAJ |
| description | The Keap1-Nrf2 pathway plays a central role in the protection of cells against oxidative and xenobiotic stresses. Nrf2 is a potent transcription activator that recognizes a unique DNA sequence known as the antioxidant response element (ARE). Under normal conditions, Nrf2 binds to Keap1 in the cytoplasm, resulting in proteasomal degradation. Following exposure to electrophiles or reactive oxygen species, Nrf2 becomes stabilized, translocates into the nucleus and activates the transcription of various cytoprotective genes. Increasing attention has been paid to the role of Nrf2 in cancer cells because the constitutive stabilization of Nrf2 has been observed in many human cancers with poor prognosis. Recent studies have shown that the antioxidant and detoxification activities of Nrf2 confer chemo- and radio-resistance to cancer cells. In this review, we provide an overview of the Keap1-Nrf2 system and discuss its role under physiological and pathological conditions, including cancers. We also introduce the results of our recent study describing Nrf2 function in the metabolism of cancer cells. Nrf2 likely confers a growth advantage to cancer cells through enhancing cytoprotection and anabolism. Finally, we discuss the possible impact of Nrf2 inhibitors on cancer therapy. |
| first_indexed | 2024-04-12T16:53:29Z |
| format | Article |
| id | doaj.art-1cf2daa998d2444089b046eee35055e6 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T16:53:29Z |
| publishDate | 2012-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-1cf2daa998d2444089b046eee35055e62022-12-22T03:24:19ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2012-12-01210.3389/fonc.2012.0020035319The Keap1-Nrf2 system in cancers: Stress response and anabolic metabolismYoichiro eMitsuishi0Hozumi eMotohashi1Masayuki eYamamoto2Tohoku University Graduate School of MedicineTohoku University Graduate School of MedicineTohoku University Graduate School of MedicineThe Keap1-Nrf2 pathway plays a central role in the protection of cells against oxidative and xenobiotic stresses. Nrf2 is a potent transcription activator that recognizes a unique DNA sequence known as the antioxidant response element (ARE). Under normal conditions, Nrf2 binds to Keap1 in the cytoplasm, resulting in proteasomal degradation. Following exposure to electrophiles or reactive oxygen species, Nrf2 becomes stabilized, translocates into the nucleus and activates the transcription of various cytoprotective genes. Increasing attention has been paid to the role of Nrf2 in cancer cells because the constitutive stabilization of Nrf2 has been observed in many human cancers with poor prognosis. Recent studies have shown that the antioxidant and detoxification activities of Nrf2 confer chemo- and radio-resistance to cancer cells. In this review, we provide an overview of the Keap1-Nrf2 system and discuss its role under physiological and pathological conditions, including cancers. We also introduce the results of our recent study describing Nrf2 function in the metabolism of cancer cells. Nrf2 likely confers a growth advantage to cancer cells through enhancing cytoprotection and anabolism. Finally, we discuss the possible impact of Nrf2 inhibitors on cancer therapy.http://journal.frontiersin.org/Journal/10.3389/fonc.2012.00200/fullGlutathionestress responsetranredox homeostasispurine nucleotide |
| spellingShingle | Yoichiro eMitsuishi Hozumi eMotohashi Masayuki eYamamoto The Keap1-Nrf2 system in cancers: Stress response and anabolic metabolism Frontiers in Oncology Glutathione stress response tran redox homeostasis purine nucleotide |
| title | The Keap1-Nrf2 system in cancers: Stress response and anabolic metabolism |
| title_full | The Keap1-Nrf2 system in cancers: Stress response and anabolic metabolism |
| title_fullStr | The Keap1-Nrf2 system in cancers: Stress response and anabolic metabolism |
| title_full_unstemmed | The Keap1-Nrf2 system in cancers: Stress response and anabolic metabolism |
| title_short | The Keap1-Nrf2 system in cancers: Stress response and anabolic metabolism |
| title_sort | keap1 nrf2 system in cancers stress response and anabolic metabolism |
| topic | Glutathione stress response tran redox homeostasis purine nucleotide |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2012.00200/full |
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