Polyanions provide selective control of APC/C interactions with the activator subunit
Open Access
- 20 December 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Communications
- Vol. 10 (1), 1-12
- https://doi.org/10.1038/s41467-019-13864-1
Abstract
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.Keywords
Funding Information
- U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (R35-GM118053)
This publication has 61 references indexed in Scilit:
- Insights into Degron Recognition by APC/C Coactivators from the Structure of an Acm1-Cdh1 ComplexMolecular Cell, 2013
- The APC/C Subunit Mnd2/Apc15 Promotes Cdc20 Autoubiquitination and Spindle Assembly Checkpoint InactivationMolecular Cell, 2012
- APC15 mediates CDC20 autoubiquitylation by APC/CMCC and disassembly of the mitotic checkpoint complexNature Structural & Molecular Biology, 2012
- Ubiquitination of Cdc20 by the APC Occurs through an Intramolecular MechanismCurrent Biology, 2011
- Mechanisms of pseudosubstrate inhibition of the anaphase promoting complex by Acm1The EMBO Journal, 2011
- Structures of APC/CCdh1 with substrates identify Cdh1 and Apc10 as the D-box co-receptorNature, 2010
- Analysis of Activator-Binding Sites on the APC/C Supports a Cooperative Substrate-Binding MechanismMolecular Cell, 2009
- An architectural map of the anaphase-promoting complexJournal of Bone and Joint Surgery, 2006
- The WD40 Propeller Domain of Cdh1 Functions as a Destruction Box Receptor for APC/C SubstratesMolecular Cell, 2005
- Co-variation of tRNA Abundance and Codon Usage inEscherichia coliat Different Growth RatesJournal of Molecular Biology, 1996