Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere

Yuichiro Asai, Koh Fukuchi, Yuji Tanno, Saki Koitabashi-Kiyozuka, Tatsuyuki Kiyozuka, Yuko Noda, Rieko Matsumura, Tetsuo Koizumi, Atsushi Watanabe, Kyosuke Nagata, Yoshinori Watanabe, Yasuhiko Terada

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)3223-3236
Number of pages14
JournalThe Journal of cell biology
Volume218
Issue number10
DOIs
Publication statusPublished - 2019 Oct 7

Fingerprint

Aurora Kinase B
Kinetochores
Centromere
Phosphorylation
Microtubules
Chromosomes
Chromosomal Instability
Chromosome Segregation
Oncogene Proteins
Aneuploidy
Phosphoric Monoester Hydrolases

ASJC Scopus subject areas

  • Cell Biology

Cite this

Asai, Y., Fukuchi, K., Tanno, Y., Koitabashi-Kiyozuka, S., Kiyozuka, T., Noda, Y., ... Terada, Y. (2019). Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere. The Journal of cell biology, 218(10), 3223-3236. https://doi.org/10.1083/jcb.201811060

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.

In: The Journal of cell biology, Vol. 218, No. 10, 07.10.2019, p. 3223-3236.

Research output: Contribution to journalArticle

Asai, Y, Fukuchi, K, Tanno, Y, Koitabashi-Kiyozuka, S, Kiyozuka, T, Noda, Y, Matsumura, R, Koizumi, T, Watanabe, A, Nagata, K, Watanabe, Y & Terada, Y 2019, 'Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere', The Journal of cell biology, vol. 218, no. 10, pp. 3223-3236. https://doi.org/10.1083/jcb.201811060
Asai Y, Fukuchi K, Tanno Y, Koitabashi-Kiyozuka S, Kiyozuka T, Noda Y et al. Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere. The Journal of cell biology. 2019 Oct 7;218(10):3223-3236. https://doi.org/10.1083/jcb.201811060
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. In: The Journal of cell biology. 2019 ; Vol. 218, No. 10. pp. 3223-3236.
@article{8f67510646054e028550c3b264b9e5c8,
title = "Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere",
abstract = "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.",
author = "Yuichiro Asai and Koh Fukuchi and Yuji Tanno and Saki Koitabashi-Kiyozuka and Tatsuyuki Kiyozuka and Yuko Noda and Rieko Matsumura and Tetsuo Koizumi and Atsushi Watanabe and Kyosuke Nagata and Yoshinori Watanabe and Yasuhiko Terada",
year = "2019",
month = "10",
day = "7",
doi = "10.1083/jcb.201811060",
language = "English",
volume = "218",
pages = "3223--3236",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "10",

}

TY - JOUR

T1 - Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere

AU - Asai, Yuichiro

AU - Fukuchi, Koh

AU - Tanno, Yuji

AU - Koitabashi-Kiyozuka, Saki

AU - Kiyozuka, Tatsuyuki

AU - Noda, Yuko

AU - Matsumura, Rieko

AU - Koizumi, Tetsuo

AU - Watanabe, Atsushi

AU - Nagata, Kyosuke

AU - Watanabe, Yoshinori

AU - Terada, Yasuhiko

PY - 2019/10/7

Y1 - 2019/10/7

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85072994971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85072994971&partnerID=8YFLogxK

U2 - 10.1083/jcb.201811060

DO - 10.1083/jcb.201811060

M3 - Article

C2 - 31527146

AN - SCOPUS:85072994971

VL - 218

SP - 3223

EP - 3236

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 10

ER -