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PIWIL1 suppresses circadian rhythms through GSK3β‐induced phosphorylation and degradation of CLOCK and BMAL1 in cancer cells
Circadian rhythms are maintained by series of circadian clock proteins, and post‐translation modifications of clock proteins significantly contribute to regulating circadian clock. However, the underlying upstream mechanism of circadian genes that are responsible for circadian rhythms in cancer cell...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584488/ https://www.ncbi.nlm.nih.gov/pubmed/31099187 http://dx.doi.org/10.1111/jcmm.14377 |
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author | Tan, Hao Zhu, Yingchuan Zheng, Xulei Lu, Yilu Tao, Dachang Liu, Yunqiang Ma, Yongxin |
author_facet | Tan, Hao Zhu, Yingchuan Zheng, Xulei Lu, Yilu Tao, Dachang Liu, Yunqiang Ma, Yongxin |
author_sort | Tan, Hao |
collection | PubMed |
description | Circadian rhythms are maintained by series of circadian clock proteins, and post‐translation modifications of clock proteins significantly contribute to regulating circadian clock. However, the underlying upstream mechanism of circadian genes that are responsible for circadian rhythms in cancer cells remains unknown. PIWIL1 participates in many physiological processes and current discoveries have shown that PIWIL1 is involved in tumorigenesis in various cancers. Here we report that PIWIL1 can suppress circadian rhythms in cancer cells. Mechanistically, by promoting SRC interacting with PI3K, PIWIL1 can activate PI3K‐AKT signalling pathway to phosphorylate and inactivate GSK3β, repressing GSK3β‐induced phosphorylation and ubiquitination of CLOCK and BMAL1. Simultaneously, together with CLOCK/BMAL1 complex, PIWIL1 can bind with E‐BOX region to suppress transcriptional activities of clock‐controlled genes promoters. Collectively, our findings first demonstrate that PIWIL1 negatively regulates circadian rhythms via two pathways, providing molecular connection between dysfunction of circadian rhythms and tumorigenesis. |
format | Online Article Text |
id | pubmed-6584488 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-65844882019-07-01 PIWIL1 suppresses circadian rhythms through GSK3β‐induced phosphorylation and degradation of CLOCK and BMAL1 in cancer cells Tan, Hao Zhu, Yingchuan Zheng, Xulei Lu, Yilu Tao, Dachang Liu, Yunqiang Ma, Yongxin J Cell Mol Med Original Articles Circadian rhythms are maintained by series of circadian clock proteins, and post‐translation modifications of clock proteins significantly contribute to regulating circadian clock. However, the underlying upstream mechanism of circadian genes that are responsible for circadian rhythms in cancer cells remains unknown. PIWIL1 participates in many physiological processes and current discoveries have shown that PIWIL1 is involved in tumorigenesis in various cancers. Here we report that PIWIL1 can suppress circadian rhythms in cancer cells. Mechanistically, by promoting SRC interacting with PI3K, PIWIL1 can activate PI3K‐AKT signalling pathway to phosphorylate and inactivate GSK3β, repressing GSK3β‐induced phosphorylation and ubiquitination of CLOCK and BMAL1. Simultaneously, together with CLOCK/BMAL1 complex, PIWIL1 can bind with E‐BOX region to suppress transcriptional activities of clock‐controlled genes promoters. Collectively, our findings first demonstrate that PIWIL1 negatively regulates circadian rhythms via two pathways, providing molecular connection between dysfunction of circadian rhythms and tumorigenesis. John Wiley and Sons Inc. 2019-05-16 2019-07 /pmc/articles/PMC6584488/ /pubmed/31099187 http://dx.doi.org/10.1111/jcmm.14377 Text en © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Articles Tan, Hao Zhu, Yingchuan Zheng, Xulei Lu, Yilu Tao, Dachang Liu, Yunqiang Ma, Yongxin PIWIL1 suppresses circadian rhythms through GSK3β‐induced phosphorylation and degradation of CLOCK and BMAL1 in cancer cells |
title | PIWIL1 suppresses circadian rhythms through GSK3β‐induced phosphorylation and degradation of CLOCK and BMAL1 in cancer cells |
title_full | PIWIL1 suppresses circadian rhythms through GSK3β‐induced phosphorylation and degradation of CLOCK and BMAL1 in cancer cells |
title_fullStr | PIWIL1 suppresses circadian rhythms through GSK3β‐induced phosphorylation and degradation of CLOCK and BMAL1 in cancer cells |
title_full_unstemmed | PIWIL1 suppresses circadian rhythms through GSK3β‐induced phosphorylation and degradation of CLOCK and BMAL1 in cancer cells |
title_short | PIWIL1 suppresses circadian rhythms through GSK3β‐induced phosphorylation and degradation of CLOCK and BMAL1 in cancer cells |
title_sort | piwil1 suppresses circadian rhythms through gsk3β‐induced phosphorylation and degradation of clock and bmal1 in cancer cells |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584488/ https://www.ncbi.nlm.nih.gov/pubmed/31099187 http://dx.doi.org/10.1111/jcmm.14377 |
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