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Preservation of circadian rhythms by the protein folding chaperone, BiP
Dysregulation of collagen synthesis is associated with disease progression in cancer and fibrosis. Collagen synthesis is coordinated with the circadian clock, which in cancer cells is, curiously, deregulated by endoplasmic reticulum (ER) stress. We hypothesized interplay between circadian rhythm, co...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Federation of American Societies for Experimental Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529331/ https://www.ncbi.nlm.nih.gov/pubmed/30888851 http://dx.doi.org/10.1096/fj.201802366RR |
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author | Pickard, Adam Chang, Joan Alachkar, Nissrin Calverley, Ben Garva, Richa Arvan, Peter Meng, Qing-Jun Kadler, Karl E. |
author_facet | Pickard, Adam Chang, Joan Alachkar, Nissrin Calverley, Ben Garva, Richa Arvan, Peter Meng, Qing-Jun Kadler, Karl E. |
author_sort | Pickard, Adam |
collection | PubMed |
description | Dysregulation of collagen synthesis is associated with disease progression in cancer and fibrosis. Collagen synthesis is coordinated with the circadian clock, which in cancer cells is, curiously, deregulated by endoplasmic reticulum (ER) stress. We hypothesized interplay between circadian rhythm, collagen synthesis, and ER stress in normal cells. Here we show that fibroblasts with ER stress lack circadian rhythms in gene expression upon clock-synchronizing time cues. Overexpression of binding immunoglobulin protein (BiP) or treatment with chemical chaperones strengthens the oscillation amplitude of circadian rhythms. The significance of these findings was explored in tendon, where we showed that BiP expression is ramped preemptively prior to a surge in collagen synthesis at night, thereby preventing protein misfolding and ER stress. In turn, this forestalls activation of the unfolded protein response in order for circadian rhythms to be maintained. Thus, targeting ER stress could be used to modulate circadian rhythm and restore collagen homeostasis in disease.—Pickard, A., Chang, J., Alachkar, N., Calverley, B., Garva, R., Arvan, P., Meng, Q.-J., Kadler, K. E. Preservation of circadian rhythms by the protein folding chaperone, BiP. |
format | Online Article Text |
id | pubmed-6529331 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Federation of American Societies for Experimental Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-65293312020-03-19 Preservation of circadian rhythms by the protein folding chaperone, BiP Pickard, Adam Chang, Joan Alachkar, Nissrin Calverley, Ben Garva, Richa Arvan, Peter Meng, Qing-Jun Kadler, Karl E. FASEB J Research Dysregulation of collagen synthesis is associated with disease progression in cancer and fibrosis. Collagen synthesis is coordinated with the circadian clock, which in cancer cells is, curiously, deregulated by endoplasmic reticulum (ER) stress. We hypothesized interplay between circadian rhythm, collagen synthesis, and ER stress in normal cells. Here we show that fibroblasts with ER stress lack circadian rhythms in gene expression upon clock-synchronizing time cues. Overexpression of binding immunoglobulin protein (BiP) or treatment with chemical chaperones strengthens the oscillation amplitude of circadian rhythms. The significance of these findings was explored in tendon, where we showed that BiP expression is ramped preemptively prior to a surge in collagen synthesis at night, thereby preventing protein misfolding and ER stress. In turn, this forestalls activation of the unfolded protein response in order for circadian rhythms to be maintained. Thus, targeting ER stress could be used to modulate circadian rhythm and restore collagen homeostasis in disease.—Pickard, A., Chang, J., Alachkar, N., Calverley, B., Garva, R., Arvan, P., Meng, Q.-J., Kadler, K. E. Preservation of circadian rhythms by the protein folding chaperone, BiP. Federation of American Societies for Experimental Biology 2019-06 2019-03-19 /pmc/articles/PMC6529331/ /pubmed/30888851 http://dx.doi.org/10.1096/fj.201802366RR Text en © The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Pickard, Adam Chang, Joan Alachkar, Nissrin Calverley, Ben Garva, Richa Arvan, Peter Meng, Qing-Jun Kadler, Karl E. Preservation of circadian rhythms by the protein folding chaperone, BiP |
title | Preservation of circadian rhythms by the protein folding chaperone, BiP |
title_full | Preservation of circadian rhythms by the protein folding chaperone, BiP |
title_fullStr | Preservation of circadian rhythms by the protein folding chaperone, BiP |
title_full_unstemmed | Preservation of circadian rhythms by the protein folding chaperone, BiP |
title_short | Preservation of circadian rhythms by the protein folding chaperone, BiP |
title_sort | preservation of circadian rhythms by the protein folding chaperone, bip |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529331/ https://www.ncbi.nlm.nih.gov/pubmed/30888851 http://dx.doi.org/10.1096/fj.201802366RR |
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