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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2019
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.
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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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