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Polyanions provide selective control of APC/C interactions with the activator subunit
Transient interactions between the anaphase-promoting complex/cyclosome (APC/C) and its activator subunit Cdc20 or Cdh1 generate oscillations in ubiquitylation activity necessary to maintain the order of cell cycle events. Activator binds the APC/C with high affinity and exhibits negligible dissocia...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925294/ https://www.ncbi.nlm.nih.gov/pubmed/31862931 http://dx.doi.org/10.1038/s41467-019-13864-1 |
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author | Mizrak, Arda Morgan, David O. |
author_facet | Mizrak, Arda Morgan, David O. |
author_sort | Mizrak, Arda |
collection | PubMed |
description | Transient interactions between the anaphase-promoting complex/cyclosome (APC/C) and its activator subunit Cdc20 or Cdh1 generate oscillations in ubiquitylation activity necessary to maintain the order of cell cycle events. Activator binds the APC/C with high affinity and exhibits negligible dissociation kinetics in vitro, and it is not clear how the rapid turnover of APC/C-activator complexes is achieved in vivo. Here, we describe a mechanism that controls APC/C-activator interactions based on the availability of substrates. We find that APC/C-activator dissociation is stimulated by abundant cellular polyanions such as nucleic acids and polyphosphate. Polyanions also interfere with substrate ubiquitylation. However, engagement with high-affinity substrate blocks the inhibitory effects of polyanions on activator binding and APC/C activity. We propose that this mechanism amplifies the effects of substrate affinity on APC/C function, stimulating processive ubiquitylation of high-affinity substrates and suppressing ubiquitylation of low-affinity substrates. |
format | Online Article Text |
id | pubmed-6925294 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-69252942019-12-22 Polyanions provide selective control of APC/C interactions with the activator subunit Mizrak, Arda Morgan, David O. Nat Commun Article Transient interactions between the anaphase-promoting complex/cyclosome (APC/C) and its activator subunit Cdc20 or Cdh1 generate oscillations in ubiquitylation activity necessary to maintain the order of cell cycle events. Activator binds the APC/C with high affinity and exhibits negligible dissociation kinetics in vitro, and it is not clear how the rapid turnover of APC/C-activator complexes is achieved in vivo. Here, we describe a mechanism that controls APC/C-activator interactions based on the availability of substrates. We find that APC/C-activator dissociation is stimulated by abundant cellular polyanions such as nucleic acids and polyphosphate. Polyanions also interfere with substrate ubiquitylation. However, engagement with high-affinity substrate blocks the inhibitory effects of polyanions on activator binding and APC/C activity. We propose that this mechanism amplifies the effects of substrate affinity on APC/C function, stimulating processive ubiquitylation of high-affinity substrates and suppressing ubiquitylation of low-affinity substrates. Nature Publishing Group UK 2019-12-20 /pmc/articles/PMC6925294/ /pubmed/31862931 http://dx.doi.org/10.1038/s41467-019-13864-1 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Mizrak, Arda Morgan, David O. Polyanions provide selective control of APC/C interactions with the activator subunit |
title | Polyanions provide selective control of APC/C interactions with the activator subunit |
title_full | Polyanions provide selective control of APC/C interactions with the activator subunit |
title_fullStr | Polyanions provide selective control of APC/C interactions with the activator subunit |
title_full_unstemmed | Polyanions provide selective control of APC/C interactions with the activator subunit |
title_short | Polyanions provide selective control of APC/C interactions with the activator subunit |
title_sort | polyanions provide selective control of apc/c interactions with the activator subunit |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6925294/ https://www.ncbi.nlm.nih.gov/pubmed/31862931 http://dx.doi.org/10.1038/s41467-019-13864-1 |
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