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

研究成果: Article

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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.

元の言語English
ページ(範囲)3223-3236
ページ数14
ジャーナルJournal of Cell Biology
218
発行部数10
DOI
出版物ステータスPublished - 2019 10 7

ASJC Scopus subject areas

  • Cell Biology

フィンガープリント Aurora B kinase activity is regulated by SET/TAF1 on Sgo2 at the inner centromere' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

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    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. Journal of Cell Biology, 218(10), 3223-3236. https://doi.org/10.1083/JCB.201811060