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USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation

Correct segregation of the mitotic chromosomes into daughter cells is a highly regulated process critical to safeguard genome stability. During M phase the spindle assembly checkpoint (SAC) ensures that all kinetochores are correctly attached before its inactivation allows progression into anaphase....

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Autores principales: Stockum, Anna, Snijders, Ambrosius P., Maertens, Goedele N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749825/
https://www.ncbi.nlm.nih.gov/pubmed/29293652
http://dx.doi.org/10.1371/journal.pone.0190513
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author Stockum, Anna
Snijders, Ambrosius P.
Maertens, Goedele N.
author_facet Stockum, Anna
Snijders, Ambrosius P.
Maertens, Goedele N.
author_sort Stockum, Anna
collection PubMed
description Correct segregation of the mitotic chromosomes into daughter cells is a highly regulated process critical to safeguard genome stability. During M phase the spindle assembly checkpoint (SAC) ensures that all kinetochores are correctly attached before its inactivation allows progression into anaphase. Upon SAC inactivation, the anaphase promoting complex/cyclosome (APC/C) E3 ligase ubiquitinates and targets cyclin B and securin for proteasomal degradation. Here, we describe the identification of Ribonucleic Acid Export protein 1 (RAE1), a protein previously shown to be involved in SAC regulation and bipolar spindle formation, as a novel substrate of the deubiquitinating enzyme (DUB) Ubiquitin Specific Protease 11 (USP11). Lentiviral knock-down of USP11 or RAE1 in U2OS cells drastically reduces cell proliferation and increases multipolar spindle formation. We show that USP11 is associated with the mitotic spindle, does not regulate SAC inactivation, but controls ubiquitination of RAE1 at the mitotic spindle, hereby functionally modulating its interaction with Nuclear Mitotic Apparatus protein (NuMA).
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spelling pubmed-57498252018-01-26 USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation Stockum, Anna Snijders, Ambrosius P. Maertens, Goedele N. PLoS One Research Article Correct segregation of the mitotic chromosomes into daughter cells is a highly regulated process critical to safeguard genome stability. During M phase the spindle assembly checkpoint (SAC) ensures that all kinetochores are correctly attached before its inactivation allows progression into anaphase. Upon SAC inactivation, the anaphase promoting complex/cyclosome (APC/C) E3 ligase ubiquitinates and targets cyclin B and securin for proteasomal degradation. Here, we describe the identification of Ribonucleic Acid Export protein 1 (RAE1), a protein previously shown to be involved in SAC regulation and bipolar spindle formation, as a novel substrate of the deubiquitinating enzyme (DUB) Ubiquitin Specific Protease 11 (USP11). Lentiviral knock-down of USP11 or RAE1 in U2OS cells drastically reduces cell proliferation and increases multipolar spindle formation. We show that USP11 is associated with the mitotic spindle, does not regulate SAC inactivation, but controls ubiquitination of RAE1 at the mitotic spindle, hereby functionally modulating its interaction with Nuclear Mitotic Apparatus protein (NuMA). Public Library of Science 2018-01-02 /pmc/articles/PMC5749825/ /pubmed/29293652 http://dx.doi.org/10.1371/journal.pone.0190513 Text en © 2018 Stockum et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Stockum, Anna
Snijders, Ambrosius P.
Maertens, Goedele N.
USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation
title USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation
title_full USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation
title_fullStr USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation
title_full_unstemmed USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation
title_short USP11 deubiquitinates RAE1 and plays a key role in bipolar spindle formation
title_sort usp11 deubiquitinates rae1 and plays a key role in bipolar spindle formation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749825/
https://www.ncbi.nlm.nih.gov/pubmed/29293652
http://dx.doi.org/10.1371/journal.pone.0190513
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