biostudies-literatureMizrak AU.S. Department of Health & Human Services | NIH | National Institute of General Medical SciencesNIGMS NIH HHS5807https://www.ebi.ac.uk/biostudies/studies/S-EPMC6925294biostudies-literatureUnknown10(1)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 pNature communicationsPolyanions provide selective control of APC/C interactions with the activator subunit.PMC6925294R35-GM118053R35 GM118053Mizrak AMorgan DOfalsePolyanions 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 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 p2019-01-01T00:00:00Z2019 Dec2025-04-18T18:40:35.644Z2020-05-22T00:09:39ZS-EPMC69252943186293110.1038/s41467-019-13864-1