NRF2 and Primary Cilia: An Emerging Partnership
When not dividing, many cell types target their centrosome to the plasma membrane, where it nucleates assembly of a primary cilium, an antenna-like signaling structure consisting of nine concentric microtubule pairs surrounded by membrane. Primary cilia play important pathophysiological roles in man...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Antioxidants |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3921/9/6/475 |
| _version_ | 1797566344661565440 |
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| author | Ana Martin-Hurtado Isabel Lastres-Becker Antonio Cuadrado Francesc R. Garcia-Gonzalo |
| author_facet | Ana Martin-Hurtado Isabel Lastres-Becker Antonio Cuadrado Francesc R. Garcia-Gonzalo |
| author_sort | Ana Martin-Hurtado |
| collection | DOAJ |
| description | When not dividing, many cell types target their centrosome to the plasma membrane, where it nucleates assembly of a primary cilium, an antenna-like signaling structure consisting of nine concentric microtubule pairs surrounded by membrane. Primary cilia play important pathophysiological roles in many tissues, their dysfunction being associated with cancer and ciliopathies, a diverse group of congenital human diseases. Several recent studies have unveiled functional connections between primary cilia and NRF2 (nuclear factor erythroid 2-related factor 2), the master transcription factor orchestrating cytoprotective responses to oxidative and other cellular stresses. These NRF2-cilia relationships are reciprocal: primary cilia, by promoting autophagy, downregulate NRF2 activity. In turn, NRF2 transcriptionally regulates genes involved in ciliogenesis and Hedgehog (Hh) signaling, a cilia-dependent pathway with major roles in embryogenesis, stem cell function and tumorigenesis. Nevertheless, while we found that NRF2 stimulates ciliogenesis and Hh signaling, a more recent study reported that NRF2 negatively affects these processes. Herein, we review the available evidence linking NRF2 to primary cilia, suggest possible explanations to reconcile seemingly contradictory data, and discuss what the emerging interplay between primary cilia and NRF2 may mean for human health and disease. |
| first_indexed | 2024-03-10T19:25:38Z |
| format | Article |
| id | doaj.art-1505ce99ac204d65831792967247aaf1 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T19:25:38Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-1505ce99ac204d65831792967247aaf12023-11-20T02:34:14ZengMDPI AGAntioxidants2076-39212020-06-019647510.3390/antiox9060475NRF2 and Primary Cilia: An Emerging PartnershipAna Martin-Hurtado0Isabel Lastres-Becker1Antonio Cuadrado2Francesc R. Garcia-Gonzalo3Instituto de Investigaciones Biomédicas Alberto Sols (IIBM), UAM-CSIC, 28029 Madrid, SpainInstituto de Investigaciones Biomédicas Alberto Sols (IIBM), UAM-CSIC, 28029 Madrid, SpainInstituto de Investigaciones Biomédicas Alberto Sols (IIBM), UAM-CSIC, 28029 Madrid, SpainInstituto de Investigaciones Biomédicas Alberto Sols (IIBM), UAM-CSIC, 28029 Madrid, SpainWhen not dividing, many cell types target their centrosome to the plasma membrane, where it nucleates assembly of a primary cilium, an antenna-like signaling structure consisting of nine concentric microtubule pairs surrounded by membrane. Primary cilia play important pathophysiological roles in many tissues, their dysfunction being associated with cancer and ciliopathies, a diverse group of congenital human diseases. Several recent studies have unveiled functional connections between primary cilia and NRF2 (nuclear factor erythroid 2-related factor 2), the master transcription factor orchestrating cytoprotective responses to oxidative and other cellular stresses. These NRF2-cilia relationships are reciprocal: primary cilia, by promoting autophagy, downregulate NRF2 activity. In turn, NRF2 transcriptionally regulates genes involved in ciliogenesis and Hedgehog (Hh) signaling, a cilia-dependent pathway with major roles in embryogenesis, stem cell function and tumorigenesis. Nevertheless, while we found that NRF2 stimulates ciliogenesis and Hh signaling, a more recent study reported that NRF2 negatively affects these processes. Herein, we review the available evidence linking NRF2 to primary cilia, suggest possible explanations to reconcile seemingly contradictory data, and discuss what the emerging interplay between primary cilia and NRF2 may mean for human health and disease.https://www.mdpi.com/2076-3921/9/6/475NRF2primary ciliahedgehog signalingciliogenesisciliopathycancer |
| spellingShingle | Ana Martin-Hurtado Isabel Lastres-Becker Antonio Cuadrado Francesc R. Garcia-Gonzalo NRF2 and Primary Cilia: An Emerging Partnership Antioxidants NRF2 primary cilia hedgehog signaling ciliogenesis ciliopathy cancer |
| title | NRF2 and Primary Cilia: An Emerging Partnership |
| title_full | NRF2 and Primary Cilia: An Emerging Partnership |
| title_fullStr | NRF2 and Primary Cilia: An Emerging Partnership |
| title_full_unstemmed | NRF2 and Primary Cilia: An Emerging Partnership |
| title_short | NRF2 and Primary Cilia: An Emerging Partnership |
| title_sort | nrf2 and primary cilia an emerging partnership |
| topic | NRF2 primary cilia hedgehog signaling ciliogenesis ciliopathy cancer |
| url | https://www.mdpi.com/2076-3921/9/6/475 |
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