The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4
In budding yeast, a surveillance mechanism known as the spindle position checkpoint (SPOC) ensures accurate genome partitioning. In the event of spindle misposition, the checkpoint delays exit from mitosis by restraining the activity of the mitotic exit network (MEN). To date, the only component of...
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Cold Spring Harbor Laboratory Press
2013
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Online Access: | http://hdl.handle.net/1721.1/77594 https://orcid.org/0000-0001-9837-0314 |
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author | Chan, Leon Y. Amon, Angelika B |
author2 | Koch Institute for Integrative Cancer Research at MIT |
author_facet | Koch Institute for Integrative Cancer Research at MIT Chan, Leon Y. Amon, Angelika B |
author_sort | Chan, Leon Y. |
collection | MIT |
description | In budding yeast, a surveillance mechanism known as the spindle position checkpoint (SPOC) ensures accurate genome partitioning. In the event of spindle misposition, the checkpoint delays exit from mitosis by restraining the activity of the mitotic exit network (MEN). To date, the only component of the checkpoint to be identified is the protein kinase Kin4. Furthermore, how the kinase is regulated by spindle position is not known. Here, we identify the protein phosphatase 2A (PP2A) in complex with the regulatory subunit Rts1 as a component of the SPOC. Loss of PP2A-Rts1 function abrogates the SPOC but not other mitotic checkpoints. We further show that the protein phosphatase functions upstream of Kin4, regulating the kinase's phosphorylation and localization during an unperturbed cell cycle and during SPOC activation, thus defining the phosphatase as a key regulator of SPOC function. |
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id | mit-1721.1/77594 |
institution | Massachusetts Institute of Technology |
language | en_US |
last_indexed | 2024-09-23T08:10:52Z |
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spelling | mit-1721.1/775942022-09-30T08:06:01Z The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4 Chan, Leon Y. Amon, Angelika B Koch Institute for Integrative Cancer Research at MIT Amon, Angelika B. Amon, Angelika B. Chan, Leon Y. In budding yeast, a surveillance mechanism known as the spindle position checkpoint (SPOC) ensures accurate genome partitioning. In the event of spindle misposition, the checkpoint delays exit from mitosis by restraining the activity of the mitotic exit network (MEN). To date, the only component of the checkpoint to be identified is the protein kinase Kin4. Furthermore, how the kinase is regulated by spindle position is not known. Here, we identify the protein phosphatase 2A (PP2A) in complex with the regulatory subunit Rts1 as a component of the SPOC. Loss of PP2A-Rts1 function abrogates the SPOC but not other mitotic checkpoints. We further show that the protein phosphatase functions upstream of Kin4, regulating the kinase's phosphorylation and localization during an unperturbed cell cycle and during SPOC activation, thus defining the phosphatase as a key regulator of SPOC function. National Science Foundation (U.S.) (Predoctoral Fellowship) National Institutes of Health (U.S.) (grant GM056800) Howard Hughes Medical Institute (Investigator) 2013-03-06T22:00:37Z 2013-03-06T22:00:37Z 2009-07 Article http://purl.org/eprint/type/JournalArticle 0890-9369 1549-5477 http://hdl.handle.net/1721.1/77594 Chan, L. Y., and A. Amon. “The Protein Phosphatase 2A Functions in the Spindle Position Checkpoint by Regulating the Checkpoint Kinase Kin4.” Genes & Development 23.14 (2009): 1639–1649. CrossRef. Web. https://orcid.org/0000-0001-9837-0314 en_US http://dx.doi.org/10.1101/gad.1804609 Genes & Development Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf Cold Spring Harbor Laboratory Press Amon via Jennifer Cimino |
spellingShingle | Chan, Leon Y. Amon, Angelika B The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4 |
title | The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4 |
title_full | The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4 |
title_fullStr | The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4 |
title_full_unstemmed | The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4 |
title_short | The protein phosphatase 2A functions in the spindle position checkpoint by regulating the checkpoint kinase Kin4 |
title_sort | protein phosphatase 2a functions in the spindle position checkpoint by regulating the checkpoint kinase kin4 |
url | http://hdl.handle.net/1721.1/77594 https://orcid.org/0000-0001-9837-0314 |
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