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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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Bibliographic Details
Published in:The Journal of cell biology 2019-10, Vol.218 (10), p.3223-3236
Main Authors: 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
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Language:English
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201811060