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Chromosome alignment‐maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl‐1 expression
Antimitotic drugs such as vinca alkaloids and taxanes cause mitotic cell death after prolonged mitotic arrest. However, a fraction of cells escape from mitotic arrest by undergoing mitotic slippage, which is related to resistance to antimitotic drugs. Tipping the balance to mitotic cell death thus c...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409433/ https://www.ncbi.nlm.nih.gov/pubmed/34107118 http://dx.doi.org/10.1111/cas.15018 |
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author | Hino, Maho Iemura, Kenji Ikeda, Masanori Itoh, Go Tanaka, Kozo |
author_facet | Hino, Maho Iemura, Kenji Ikeda, Masanori Itoh, Go Tanaka, Kozo |
author_sort | Hino, Maho |
collection | PubMed |
description | Antimitotic drugs such as vinca alkaloids and taxanes cause mitotic cell death after prolonged mitotic arrest. However, a fraction of cells escape from mitotic arrest by undergoing mitotic slippage, which is related to resistance to antimitotic drugs. Tipping the balance to mitotic cell death thus can be a way to overcome the drug resistance. Here we found that depletion of a mitotic regulator, CHAMP1 (chromosome alignment‐maintaining phosphoprotein, CAMP), accelerates the timing of mitotic cell death after mitotic arrest. Live cell imaging revealed that CHAMP1‐depleted cells died earlier than mock‐treated cells in the presence of antimitotic drugs that resulted in the reduction of cells undergoing mitotic slippage. Depletion CHAMP1 reduces the expression of antiapoptotic Bcl‐2 family proteins, especially Mcl‐1. We found that CHAMP1 maintains Mcl‐1 expression both at protein and mRNA levels independently of the cell cycle. At the protein level, CHAMP1 maintains Mcl‐1 stability by suppressing proteasome‐dependent degradation. Depletion of CHAMP1 reduces cell viability, and exhibits synergistic effects with antimitotic drugs. Our data suggest that CHAMP1 plays a role in the maintenance of Mcl‐1 expression, implying that CHAMP1 can be a target to overcome the resistance to antimitotic drugs. |
format | Online Article Text |
id | pubmed-8409433 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84094332021-09-03 Chromosome alignment‐maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl‐1 expression Hino, Maho Iemura, Kenji Ikeda, Masanori Itoh, Go Tanaka, Kozo Cancer Sci Original Articles Antimitotic drugs such as vinca alkaloids and taxanes cause mitotic cell death after prolonged mitotic arrest. However, a fraction of cells escape from mitotic arrest by undergoing mitotic slippage, which is related to resistance to antimitotic drugs. Tipping the balance to mitotic cell death thus can be a way to overcome the drug resistance. Here we found that depletion of a mitotic regulator, CHAMP1 (chromosome alignment‐maintaining phosphoprotein, CAMP), accelerates the timing of mitotic cell death after mitotic arrest. Live cell imaging revealed that CHAMP1‐depleted cells died earlier than mock‐treated cells in the presence of antimitotic drugs that resulted in the reduction of cells undergoing mitotic slippage. Depletion CHAMP1 reduces the expression of antiapoptotic Bcl‐2 family proteins, especially Mcl‐1. We found that CHAMP1 maintains Mcl‐1 expression both at protein and mRNA levels independently of the cell cycle. At the protein level, CHAMP1 maintains Mcl‐1 stability by suppressing proteasome‐dependent degradation. Depletion of CHAMP1 reduces cell viability, and exhibits synergistic effects with antimitotic drugs. Our data suggest that CHAMP1 plays a role in the maintenance of Mcl‐1 expression, implying that CHAMP1 can be a target to overcome the resistance to antimitotic drugs. John Wiley and Sons Inc. 2021-07-16 2021-09 /pmc/articles/PMC8409433/ /pubmed/34107118 http://dx.doi.org/10.1111/cas.15018 Text en © 2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Original Articles Hino, Maho Iemura, Kenji Ikeda, Masanori Itoh, Go Tanaka, Kozo Chromosome alignment‐maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl‐1 expression |
title | Chromosome alignment‐maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl‐1 expression |
title_full | Chromosome alignment‐maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl‐1 expression |
title_fullStr | Chromosome alignment‐maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl‐1 expression |
title_full_unstemmed | Chromosome alignment‐maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl‐1 expression |
title_short | Chromosome alignment‐maintaining phosphoprotein CHAMP1 plays a role in cell survival through regulating Mcl‐1 expression |
title_sort | chromosome alignment‐maintaining phosphoprotein champ1 plays a role in cell survival through regulating mcl‐1 expression |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409433/ https://www.ncbi.nlm.nih.gov/pubmed/34107118 http://dx.doi.org/10.1111/cas.15018 |
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