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Thyroid Hormone Receptor α1 Follows a Cooperative CRM1/Calreticulin-mediated Nuclear Export Pathway

The thyroid hormone receptor α1 (TRα) exhibits a dual role as an activator or repressor of its target genes in response to thyroid hormone (T(3)). Previously, we have shown that TRα, formerly thought to reside solely in the nucleus bound to DNA, actually shuttles rapidly between the nucleus and cyto...

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Autores principales: Grespin, Matthew E., Bonamy, Ghislain M. C., Roggero, Vincent R., Cameron, Nicole G., Adam, Lindsay E., Atchison, Andrew P., Fratto, Victoria M., Allison, Lizabeth A.
Formato: Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2533095/
https://www.ncbi.nlm.nih.gov/pubmed/18641393
http://dx.doi.org/10.1074/jbc.M710482200
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author Grespin, Matthew E.
Bonamy, Ghislain M. C.
Roggero, Vincent R.
Cameron, Nicole G.
Adam, Lindsay E.
Atchison, Andrew P.
Fratto, Victoria M.
Allison, Lizabeth A.
author_facet Grespin, Matthew E.
Bonamy, Ghislain M. C.
Roggero, Vincent R.
Cameron, Nicole G.
Adam, Lindsay E.
Atchison, Andrew P.
Fratto, Victoria M.
Allison, Lizabeth A.
author_sort Grespin, Matthew E.
collection PubMed
description The thyroid hormone receptor α1 (TRα) exhibits a dual role as an activator or repressor of its target genes in response to thyroid hormone (T(3)). Previously, we have shown that TRα, formerly thought to reside solely in the nucleus bound to DNA, actually shuttles rapidly between the nucleus and cytoplasm. An important aspect of the shuttling activity of TRα is its ability to exit the nucleus through the nuclear pore complex. TRα export is not sensitive to treatment with the CRM1-specific inhibitor leptomycin B (LMB) in heterokaryon assays, suggesting a role for an export receptor other than CRM1. Here, we have used a combined approach of in vivo fluorescence recovery after photobleaching experiments, in vitro permeabilized cell nuclear export assays, and glutathione S-transferase pull-down assays to investigate the export pathway used by TRα. We show that, in addition to shuttling in heterokaryons, TRα shuttles rapidly in an unfused monokaryon system as well. Furthermore, our data show that TRα directly interacts with calreticulin, and point to the intriguing possibility that TRα follows a cooperative export pathway in which both calreticulin and CRM1 play a role in facilitating efficient translocation of TRα from the nucleus to cytoplasm.
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spelling pubmed-25330952008-12-18 Thyroid Hormone Receptor α1 Follows a Cooperative CRM1/Calreticulin-mediated Nuclear Export Pathway Grespin, Matthew E. Bonamy, Ghislain M. C. Roggero, Vincent R. Cameron, Nicole G. Adam, Lindsay E. Atchison, Andrew P. Fratto, Victoria M. Allison, Lizabeth A. J Biol Chem Mechanisms of Signal Transduction The thyroid hormone receptor α1 (TRα) exhibits a dual role as an activator or repressor of its target genes in response to thyroid hormone (T(3)). Previously, we have shown that TRα, formerly thought to reside solely in the nucleus bound to DNA, actually shuttles rapidly between the nucleus and cytoplasm. An important aspect of the shuttling activity of TRα is its ability to exit the nucleus through the nuclear pore complex. TRα export is not sensitive to treatment with the CRM1-specific inhibitor leptomycin B (LMB) in heterokaryon assays, suggesting a role for an export receptor other than CRM1. Here, we have used a combined approach of in vivo fluorescence recovery after photobleaching experiments, in vitro permeabilized cell nuclear export assays, and glutathione S-transferase pull-down assays to investigate the export pathway used by TRα. We show that, in addition to shuttling in heterokaryons, TRα shuttles rapidly in an unfused monokaryon system as well. Furthermore, our data show that TRα directly interacts with calreticulin, and point to the intriguing possibility that TRα follows a cooperative export pathway in which both calreticulin and CRM1 play a role in facilitating efficient translocation of TRα from the nucleus to cytoplasm. American Society for Biochemistry and Molecular Biology 2008-09-12 /pmc/articles/PMC2533095/ /pubmed/18641393 http://dx.doi.org/10.1074/jbc.M710482200 Text en Copyright © 2008, The American Society for Biochemistry and Molecular Biology, Inc. Author's Choice Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) applies to Author Choice Articles
spellingShingle Mechanisms of Signal Transduction
Grespin, Matthew E.
Bonamy, Ghislain M. C.
Roggero, Vincent R.
Cameron, Nicole G.
Adam, Lindsay E.
Atchison, Andrew P.
Fratto, Victoria M.
Allison, Lizabeth A.
Thyroid Hormone Receptor α1 Follows a Cooperative CRM1/Calreticulin-mediated Nuclear Export Pathway
title Thyroid Hormone Receptor α1 Follows a Cooperative CRM1/Calreticulin-mediated Nuclear Export Pathway
title_full Thyroid Hormone Receptor α1 Follows a Cooperative CRM1/Calreticulin-mediated Nuclear Export Pathway
title_fullStr Thyroid Hormone Receptor α1 Follows a Cooperative CRM1/Calreticulin-mediated Nuclear Export Pathway
title_full_unstemmed Thyroid Hormone Receptor α1 Follows a Cooperative CRM1/Calreticulin-mediated Nuclear Export Pathway
title_short Thyroid Hormone Receptor α1 Follows a Cooperative CRM1/Calreticulin-mediated Nuclear Export Pathway
title_sort thyroid hormone receptor α1 follows a cooperative crm1/calreticulin-mediated nuclear export pathway
topic Mechanisms of Signal Transduction
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2533095/
https://www.ncbi.nlm.nih.gov/pubmed/18641393
http://dx.doi.org/10.1074/jbc.M710482200
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