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The APC/C targets the Cep152–Cep63 complex at the centrosome to regulate mitotic spindle assembly

The control of protein abundance is a fundamental regulatory mechanism during mitosis. The anaphase-promoting complex/cyclosome (APC/C) is the main protein ubiquitin ligase responsible for the temporal regulation of mitotic progression. It has been proposed that the APC/C might fulfil other function...

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Autores principales: Tischer, Thomas, Yang, Jing, Barford, David
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Company of Biologists Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917351/
https://www.ncbi.nlm.nih.gov/pubmed/34878135
http://dx.doi.org/10.1242/jcs.259273
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author Tischer, Thomas
Yang, Jing
Barford, David
author_facet Tischer, Thomas
Yang, Jing
Barford, David
author_sort Tischer, Thomas
collection PubMed
description The control of protein abundance is a fundamental regulatory mechanism during mitosis. The anaphase-promoting complex/cyclosome (APC/C) is the main protein ubiquitin ligase responsible for the temporal regulation of mitotic progression. It has been proposed that the APC/C might fulfil other functions, including assembly of the mitotic spindle. Here, we show that the APC/C localizes to centrosomes, the organizers of the eukaryotic microtubule cytoskeleton, specifically during mitosis. Recruitment of the APC/C to spindle poles requires the centrosomal protein Cep152, and we identified Cep152 as both an APC/C interaction partner and an APC/C substrate. Previous studies have shown that Cep152 forms a complex with Cep57 and Cep63. The APC/C-mediated ubiquitylation of Cep152 at the centrosome releases Cep57 from this inhibitory complex and enables its interaction with pericentrin, a critical step in promoting microtubule nucleation. Thus, our study extends the function of the APC/C from being a regulator of mitosis to also acting as a positive governor of spindle assembly. The APC/C thereby integrates control of these two important processes in a temporal manner.
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spelling pubmed-89173512022-03-16 The APC/C targets the Cep152–Cep63 complex at the centrosome to regulate mitotic spindle assembly Tischer, Thomas Yang, Jing Barford, David J Cell Sci Research Article The control of protein abundance is a fundamental regulatory mechanism during mitosis. The anaphase-promoting complex/cyclosome (APC/C) is the main protein ubiquitin ligase responsible for the temporal regulation of mitotic progression. It has been proposed that the APC/C might fulfil other functions, including assembly of the mitotic spindle. Here, we show that the APC/C localizes to centrosomes, the organizers of the eukaryotic microtubule cytoskeleton, specifically during mitosis. Recruitment of the APC/C to spindle poles requires the centrosomal protein Cep152, and we identified Cep152 as both an APC/C interaction partner and an APC/C substrate. Previous studies have shown that Cep152 forms a complex with Cep57 and Cep63. The APC/C-mediated ubiquitylation of Cep152 at the centrosome releases Cep57 from this inhibitory complex and enables its interaction with pericentrin, a critical step in promoting microtubule nucleation. Thus, our study extends the function of the APC/C from being a regulator of mitosis to also acting as a positive governor of spindle assembly. The APC/C thereby integrates control of these two important processes in a temporal manner. The Company of Biologists Ltd 2022-01-18 /pmc/articles/PMC8917351/ /pubmed/34878135 http://dx.doi.org/10.1242/jcs.259273 Text en © 2022. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle Research Article
Tischer, Thomas
Yang, Jing
Barford, David
The APC/C targets the Cep152–Cep63 complex at the centrosome to regulate mitotic spindle assembly
title The APC/C targets the Cep152–Cep63 complex at the centrosome to regulate mitotic spindle assembly
title_full The APC/C targets the Cep152–Cep63 complex at the centrosome to regulate mitotic spindle assembly
title_fullStr The APC/C targets the Cep152–Cep63 complex at the centrosome to regulate mitotic spindle assembly
title_full_unstemmed The APC/C targets the Cep152–Cep63 complex at the centrosome to regulate mitotic spindle assembly
title_short The APC/C targets the Cep152–Cep63 complex at the centrosome to regulate mitotic spindle assembly
title_sort apc/c targets the cep152–cep63 complex at the centrosome to regulate mitotic spindle assembly
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917351/
https://www.ncbi.nlm.nih.gov/pubmed/34878135
http://dx.doi.org/10.1242/jcs.259273
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