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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...

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Autores principales: Martin-Hurtado, Ana, Lastres-Becker, Isabel, Cuadrado, Antonio, Garcia-Gonzalo, Francesc R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346227/
https://www.ncbi.nlm.nih.gov/pubmed/32498260
http://dx.doi.org/10.3390/antiox9060475
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author Martin-Hurtado, Ana
Lastres-Becker, Isabel
Cuadrado, Antonio
Garcia-Gonzalo, Francesc R.
author_facet Martin-Hurtado, Ana
Lastres-Becker, Isabel
Cuadrado, Antonio
Garcia-Gonzalo, Francesc R.
author_sort Martin-Hurtado, Ana
collection PubMed
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.
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spelling pubmed-73462272020-07-20 NRF2 and Primary Cilia: An Emerging Partnership Martin-Hurtado, Ana Lastres-Becker, Isabel Cuadrado, Antonio Garcia-Gonzalo, Francesc R. Antioxidants (Basel) Review 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. MDPI 2020-06-02 /pmc/articles/PMC7346227/ /pubmed/32498260 http://dx.doi.org/10.3390/antiox9060475 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Martin-Hurtado, Ana
Lastres-Becker, Isabel
Cuadrado, Antonio
Garcia-Gonzalo, Francesc R.
NRF2 and Primary Cilia: An Emerging Partnership
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 Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346227/
https://www.ncbi.nlm.nih.gov/pubmed/32498260
http://dx.doi.org/10.3390/antiox9060475
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