Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase
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 sub...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Rockefeller University Press
2011
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| Online Access: | http://hdl.handle.net/1721.1/60658 https://orcid.org/0000-0002-3829-5612 |
| _version_ | 1826204268067028992 |
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| author | Liu, Dan Vleugel, Mathijs Backer, Chelsea B. Hori, Tetsuya Fukagawa, Tatsuo Lampson, Michael A. Cheeseman, Iain M |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Liu, Dan Vleugel, Mathijs Backer, Chelsea B. Hori, Tetsuya Fukagawa, Tatsuo Lampson, Michael A. Cheeseman, Iain M |
| author_sort | Liu, Dan |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:51:36Z |
| format | Article |
| id | mit-1721.1/60658 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:51:36Z |
| publishDate | 2011 |
| publisher | Rockefeller University Press |
| record_format | dspace |
| spelling | mit-1721.1/606582022-09-28T10:30:25Z Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase Liu, Dan Vleugel, Mathijs Backer, Chelsea B. Hori, Tetsuya Fukagawa, Tatsuo Lampson, Michael A. Cheeseman, Iain M Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Cheeseman, Iain McPherson Vleugel, Mathijs Cheeseman, Iain McPherson Backer, Chelsea B. 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. National Institutes of Health (U.S) (GM083988) National Institutes of Health (U.S) (GM088313) Searle Scholars Program Smith Family Foundation Massachusetts Life Sciences Center Japan. Ministry of Education, Culture, Sports, Science and Technology (MEXT) 2011-01-19T13:32:01Z 2011-01-19T13:32:01Z 2010-03 2010-02 Article http://purl.org/eprint/type/JournalArticle 0021-9525 1540-8140 http://hdl.handle.net/1721.1/60658 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. 20231380 https://orcid.org/0000-0002-3829-5612 en_US http://dx.doi.org/10.1083/jcb.201001006 Journal of Cell Biology 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. application/pdf Rockefeller University Press Rockefeller UP |
| spellingShingle | Liu, Dan Vleugel, Mathijs Backer, Chelsea B. Hori, Tetsuya Fukagawa, Tatsuo Lampson, Michael A. Cheeseman, Iain M Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase |
| title | Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase |
| title_full | Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase |
| title_fullStr | Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase |
| title_full_unstemmed | Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase |
| title_short | Regulated targeting of protein phosphatase 1 to the outer kinetochore by KNL1 opposes Aurora B kinase |
| title_sort | regulated targeting of protein phosphatase 1 to the outer kinetochore by knl1 opposes aurora b kinase |
| url | http://hdl.handle.net/1721.1/60658 https://orcid.org/0000-0002-3829-5612 |
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