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Polyanions provide selective control of APC/C interactions with the activator subunit
1Department of Physiology, University of California, San Francisco, CA, 94143, USA.
Nature Communications
|December 22, 2019
Summary
Cell cycle regulation relies on the anaphase-promoting complex/cyclosome (APC/C). New findings reveal polyanions control APC/C-activator complex turnover by influencing substrate binding and ubiquitylation activity.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- The anaphase-promoting complex/cyclosome (APC/C) orchestrates cell cycle progression through regulated ubiquitylation.
- Transient interactions between APC/C and its activators (Cdc20, Cdh1) are crucial for cell cycle order.
- The mechanism for rapid in vivo turnover of high-affinity APC/C-activator complexes remains unclear.
Purpose of the Study:
- To elucidate the mechanism controlling APC/C-activator complex dissociation in vivo.
- To investigate the role of substrate availability in regulating APC/C activity.
- To understand how cellular conditions modulate APC/C function.
Main Methods:
- Investigated APC/C-activator interactions in vitro and in vivo.
- Assessed the impact of cellular polyanions (nucleic acids, polyphosphate) on complex dynamics.
- Examined the influence of substrate affinity on polyanion effects and APC/C ubiquitylation activity.
Main Results:
- Abundant cellular polyanions stimulate APC/C-activator complex dissociation.
- Polyanions inhibit substrate ubiquitylation, but this inhibition is overcome by high-affinity substrates.
- Substrate engagement blocks polyanion interference with activator binding and APC/C activity.
Conclusions:
- A novel mechanism controlling APC/C-activator interactions based on substrate availability is described.
- Cellular polyanions act as regulators of APC/C-activator turnover.
- This mechanism amplifies substrate affinity effects, ensuring processive ubiquitylation of high-affinity substrates and suppressing low-affinity ones.
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