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ERRβ splice variants differentially regulate cell cycle progression
Orphan receptors comprise nearly half of all members of the nuclear receptor superfamily. Despite having broad structural similarities to the classical estrogen receptors, estrogen-related receptors (ERRs) have their own unique DNA response elements and functions. In this study, we focus on 2 ERRβ s...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614362/ https://www.ncbi.nlm.nih.gov/pubmed/25496115 http://dx.doi.org/10.4161/15384101.2014.972886 |
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author | Heckler, Mary Mazzotta Riggins, Rebecca B |
author_facet | Heckler, Mary Mazzotta Riggins, Rebecca B |
author_sort | Heckler, Mary Mazzotta |
collection | PubMed |
description | Orphan receptors comprise nearly half of all members of the nuclear receptor superfamily. Despite having broad structural similarities to the classical estrogen receptors, estrogen-related receptors (ERRs) have their own unique DNA response elements and functions. In this study, we focus on 2 ERRβ splice variants, short form ERRβ (ERRβsf) and ERRβ2, and identify their differing roles in cell cycle regulation. Using DY131 (a synthetic agonist of ERRβ), splice-variant selective shRNA, and exogenous ERRβsf and ERRβ2 cDNAs, we demonstrate the role of ERRβsf in mediating the G1 checkpoint through p21. We also show ERRβsf is required for DY131-induced cellular senescence. A key novel finding of this study is that ERRβ2 can mediate a G2/M arrest in response to DY131. In the absence of ERRβ2, the DY131-induced G2/M arrest is reversed, and this is accompanied by p21 induction and a G1 arrest. This study illustrates novel functions for ERRβ splice variants and provides evidence for splice variant interaction. |
format | Online Article Text |
id | pubmed-4614362 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-46143622015-12-12 ERRβ splice variants differentially regulate cell cycle progression Heckler, Mary Mazzotta Riggins, Rebecca B Cell Cycle Reports Orphan receptors comprise nearly half of all members of the nuclear receptor superfamily. Despite having broad structural similarities to the classical estrogen receptors, estrogen-related receptors (ERRs) have their own unique DNA response elements and functions. In this study, we focus on 2 ERRβ splice variants, short form ERRβ (ERRβsf) and ERRβ2, and identify their differing roles in cell cycle regulation. Using DY131 (a synthetic agonist of ERRβ), splice-variant selective shRNA, and exogenous ERRβsf and ERRβ2 cDNAs, we demonstrate the role of ERRβsf in mediating the G1 checkpoint through p21. We also show ERRβsf is required for DY131-induced cellular senescence. A key novel finding of this study is that ERRβ2 can mediate a G2/M arrest in response to DY131. In the absence of ERRβ2, the DY131-induced G2/M arrest is reversed, and this is accompanied by p21 induction and a G1 arrest. This study illustrates novel functions for ERRβ splice variants and provides evidence for splice variant interaction. Taylor & Francis 2014-12-12 /pmc/articles/PMC4614362/ /pubmed/25496115 http://dx.doi.org/10.4161/15384101.2014.972886 Text en © 2015 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. |
spellingShingle | Reports Heckler, Mary Mazzotta Riggins, Rebecca B ERRβ splice variants differentially regulate cell cycle progression |
title | ERRβ splice variants differentially regulate cell cycle
progression |
title_full | ERRβ splice variants differentially regulate cell cycle
progression |
title_fullStr | ERRβ splice variants differentially regulate cell cycle
progression |
title_full_unstemmed | ERRβ splice variants differentially regulate cell cycle
progression |
title_short | ERRβ splice variants differentially regulate cell cycle
progression |
title_sort | errβ splice variants differentially regulate cell cycle
progression |
topic | Reports |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4614362/ https://www.ncbi.nlm.nih.gov/pubmed/25496115 http://dx.doi.org/10.4161/15384101.2014.972886 |
work_keys_str_mv | AT hecklermarymazzotta errbsplicevariantsdifferentiallyregulatecellcycleprogression AT rigginsrebeccab errbsplicevariantsdifferentiallyregulatecellcycleprogression |