Co-activator independent differences in how the metaphase and anaphase APC/C recognise the same substrate
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Updated: Apr 24, 2026
Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
Takahiro Matsusaka1, Maria Enquist-Newman2, David O Morgan2
1The Gurdon Institute, Tennis Court Road, Cambridge CB2 1QN, UK Department of Zoology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.
Abstract:
The Anaphase Promoting Complex or Cyclosome (APC/C) is critical to the control of mitosis. The APC/C is an ubiquitin ligase that targets specific mitotic regulators for proteolysis at distinct times in mitosis, but how this is achieved is not well understood. We have addressed this question by determining whether the same substrate, cyclin B1, is recognised in the same way by the APC/C at different times in mitosis. Unexpectedly, we find that distinct but overlapping motifs in cyclin B1 are recognised by the APC/C in metaphase compared with anaphase, and this does not depend on the exchange of Cdc20 for Cdh1. Thus, changes in APC/C substrate specificity in mitosis can potentially be conferred by altering interaction sites in addition to exchanging Cdc20 for Cdh1.
Insights
The Anaphase Promoting Complex/Cyclosome (APC/C) controls mitosis by targeting proteins for degradation. This study reveals APC/C recognizes different motifs on cyclin B1 during metaphase versus anaphase, impacting substrate specificity.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The Anaphase Promoting Complex or Cyclosome (APC/C) is a crucial ubiquitin ligase essential for regulating mitosis.
- APC/C targets key mitotic regulators for proteolysis, but the precise mechanisms of substrate recognition remain unclear.
Purpose of the Study:
- To investigate whether the Anaphase Promoting Complex/Cyclosome (APC/C) recognizes the same substrate, cyclin B1, in an identical manner throughout mitosis.
- To elucidate the mechanisms governing APC/C substrate specificity during cell division.
Main Methods:
- Comparative analysis of cyclin B1 recognition by APC/C at different mitotic stages (metaphase and anaphase).
- Investigation of the role of adaptor proteins Cdc20 and Cdh1 in mediating substrate recognition.
Main Results:
- Distinct yet overlapping motifs within cyclin B1 are recognized by APC/C during metaphase compared to anaphase.
- This differential recognition of cyclin B1 by APC/C does not rely on the exchange of Cdc20 for Cdh1.
Conclusions:
- APC/C substrate specificity can be modulated by alterations in substrate interaction sites, independent of adaptor protein exchange.
- These findings offer new insights into the dynamic regulation of mitosis by the APC/C complex.
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