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Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere
The accurate regulation of phosphorylation at the kinetochore is essential for establishing chromosome bi-orientation. Phosphorylation of kinetochore proteins by the Aurora B kinase destabilizes improper kinetochore–microtubule attachments, whereas the phosphatase PP2A has a counteracting role. Imba...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781429/ https://www.ncbi.nlm.nih.gov/pubmed/31527146 http://dx.doi.org/10.1083/jcb.201811060 |
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author | Asai, Yuichiro Fukuchi, Koh Tanno, Yuji Koitabashi-Kiyozuka, Saki Kiyozuka, Tatsuyuki Noda, Yuko Matsumura, Rieko Koizumi, Tetsuo Watanabe, Atsushi Nagata, Kyosuke Watanabe, Yoshinori Terada, Yasuhiko |
author_facet | Asai, Yuichiro Fukuchi, Koh Tanno, Yuji Koitabashi-Kiyozuka, Saki Kiyozuka, Tatsuyuki Noda, Yuko Matsumura, Rieko Koizumi, Tetsuo Watanabe, Atsushi Nagata, Kyosuke Watanabe, Yoshinori Terada, Yasuhiko |
author_sort | Asai, Yuichiro |
collection | PubMed |
description | The accurate regulation of phosphorylation at the kinetochore is essential for establishing chromosome bi-orientation. Phosphorylation of kinetochore proteins by the Aurora B kinase destabilizes improper kinetochore–microtubule attachments, whereas the phosphatase PP2A has a counteracting role. Imbalanced phosphoregulation leads to error-prone chromosome segregation and aneuploidy, a hallmark of cancer cells. However, little is known about the molecular events that control the balance of phosphorylation at the kinetochore. Here, we show that localization of SET/TAF1, an oncogene product, to centromeres maintains Aurora B kinase activity by inhibiting PP2A, thereby correcting erroneous kinetochore–microtubule attachment. SET localizes at the inner centromere by interacting directly with shugoshin 2, with SET levels declining at increased distances between kinetochore pairs, leading to establishment of chromosome bi-orientation. Moreover, SET overexpression induces chromosomal instability by disrupting kinetochore–microtubule attachment. Thus, our findings reveal the novel role of SET in fine-tuning the phosphorylation level at the kinetochore by balancing the activities of Aurora B and PP2A. |
format | Online Article Text |
id | pubmed-6781429 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-67814292020-04-07 Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere Asai, Yuichiro Fukuchi, Koh Tanno, Yuji Koitabashi-Kiyozuka, Saki Kiyozuka, Tatsuyuki Noda, Yuko Matsumura, Rieko Koizumi, Tetsuo Watanabe, Atsushi Nagata, Kyosuke Watanabe, Yoshinori Terada, Yasuhiko J Cell Biol Research Articles The accurate regulation of phosphorylation at the kinetochore is essential for establishing chromosome bi-orientation. Phosphorylation of kinetochore proteins by the Aurora B kinase destabilizes improper kinetochore–microtubule attachments, whereas the phosphatase PP2A has a counteracting role. Imbalanced phosphoregulation leads to error-prone chromosome segregation and aneuploidy, a hallmark of cancer cells. However, little is known about the molecular events that control the balance of phosphorylation at the kinetochore. Here, we show that localization of SET/TAF1, an oncogene product, to centromeres maintains Aurora B kinase activity by inhibiting PP2A, thereby correcting erroneous kinetochore–microtubule attachment. SET localizes at the inner centromere by interacting directly with shugoshin 2, with SET levels declining at increased distances between kinetochore pairs, leading to establishment of chromosome bi-orientation. Moreover, SET overexpression induces chromosomal instability by disrupting kinetochore–microtubule attachment. Thus, our findings reveal the novel role of SET in fine-tuning the phosphorylation level at the kinetochore by balancing the activities of Aurora B and PP2A. Rockefeller University Press 2019-10-07 2019-09-16 /pmc/articles/PMC6781429/ /pubmed/31527146 http://dx.doi.org/10.1083/jcb.201811060 Text en © 2019 Asai et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Asai, Yuichiro Fukuchi, Koh Tanno, Yuji Koitabashi-Kiyozuka, Saki Kiyozuka, Tatsuyuki Noda, Yuko Matsumura, Rieko Koizumi, Tetsuo Watanabe, Atsushi Nagata, Kyosuke Watanabe, Yoshinori Terada, Yasuhiko Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere |
title | Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere |
title_full | Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere |
title_fullStr | Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere |
title_full_unstemmed | Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere |
title_short | Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere |
title_sort | aurora b kinase activity is regulated by set/taf1 on sgo2 at the inner centromere |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781429/ https://www.ncbi.nlm.nih.gov/pubmed/31527146 http://dx.doi.org/10.1083/jcb.201811060 |
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