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 language | English |
|---|---|
| Pages (from-to) | 3223-3236 |
| Number of pages | 14 |
| Journal | The Journal of cell biology |
| Volume | 218 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2019 Oct 7 |
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ASJC Scopus subject areas
- Cell Biology
Cite this
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 journal › Article
}
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 -