Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase
Name
Liu-2010-Regulated targeting.pdf
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6.73 MB
Format
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Checksum (MD5)
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Author(s)
Liu, Dan
Vleugel, Mathijs
Backer, Chelsea B.
Hori, Tetsuya
Fukagawa, Tatsuo
Lampson, Michael A.
Cheeseman, Iain M
Date Issued
March 2010
Journal
Journal of Cell Biology
Publisher
Rockefeller University Press
Citation
Liu, Dan et al. “Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase.” The Journal of Cell Biology 188.6 (2010): 809 -820.
Version
Final published version
Abstract
Regulated interactions between kinetochores and spindle microtubules are essential to maintain genomic stability during chromosome segregation. The Aurora B kinase phosphorylates kinetochore substrates to destabilize kinetochore–microtubule interactions and eliminate incorrect attachments. These substrates must be dephosphorylated to stabilize correct attachments, but how opposing kinase and phosphatase activities are coordinated at the kinetochore is unknown. Here, we demonstrate that a conserved motif in the kinetochore protein KNL1 directly interacts with and targets protein phosphatase 1 (PP1) to the outer kinetochore. PP1 recruitment by KNL1 is required to dephosphorylate Aurora B substrates at kinetochores and stabilize microtubule attachments. PP1 levels at kinetochores are regulated and inversely proportional to local Aurora B activity. Indeed, we demonstrate that phosphorylation of KNL1 by Aurora B disrupts the KNL1–PP1 interaction. In total, our results support a positive feedback mechanism by which Aurora B activity at kinetochores not only targets substrates directly, but also prevents localization of the opposing phosphatase.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1083/jcb.201001006
