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Live Cell Imaging to Assess the Dynamics of Metaphase Timing and Cell Fate Following Mitotic Spindle Perturbations
Published on: September 20, 2019
An architectural map of the anaphase-promoting complex
Brian R Thornton1, Tessie M Ng, Mary E Matyskiela
1Cancer Research Institute, Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California 94115, USA.
Genes & Development
|February 17, 2006
Summary
The anaphase-promoting complex (APC) is a ubiquitin ligase. This study reveals its scaffold protein Apc1 and subunit assembly, clarifying APC function and regulation by Cdc20 and Cdh1.
Area of Science:
- Cellular biology
- Molecular genetics
- Protein biochemistry
Background:
- The anaphase-promoting complex/cyclosome (APC) is a crucial E3 ubiquitin ligase essential for cell cycle progression.
- APC is composed of 13 core subunits and regulatory proteins Cdc20 and Cdh1, but its precise architecture and subunit interactions remain incompletely understood.
Purpose of the Study:
- To elucidate the subunit architecture and assembly of the anaphase-promoting complex (APC).
- To investigate the roles of specific APC subunits and regulatory domains in APC activity and function.
Main Methods:
- Utilized a novel budding yeast strain viable without essential APC subunits.
- Performed biochemical analyses to determine subunit association and interdependence.
- Conducted enzymatic assays on purified APC complexes lacking specific subunits.
Main Results:
- Identified Apc1 as a central scaffold protein connecting two distinct subcomplexes.
- Demonstrated interdependent binding among Apc1, Apc4, Apc5, and Cdc23.
- Showed that both cullin and TPR subunits contribute to Cdh1 binding, with residual APC activity in cdc27Δ complexes dependent on Cdh1's C-box domain.
- Found the IR domain of Cdc20 to be dispensable for viability.
Conclusions:
- An updated model for APC subunit architecture and assembly has been proposed.
- Specific domains of regulatory subunits Cdh1 and Cdc20 play distinct roles in APC regulation.
- Understanding APC architecture provides insights into cell cycle control mechanisms.
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