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Updated: Jun 23, 2026
Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
Published on: September 17, 2012
Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC
Nagi G Ayad1, Susannah Rankin, Monica Murakami
1Department of Cell Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.
Abstract:
Entry into mitosis requires the activation of cdk1/cyclin B, while mitotic exit is achieved when the same kinase activity decreases, as cyclin B is degraded. Cyclin B proteolysis is mediated by the anaphase promoting complex, or APC, an E3 ligase that is active at anaphase in mitosis through G1. We have identified a G1 substrate of the APC that we have termed Tome-1, for trigger of mitotic entry. Tome-1 is a cytosolic protein required for proper activation of cdk1/cyclin B and mitotic entry. Tome-1 associates with Skp-1 and is required for degradation of the cdk1 inhibitory tyrosine kinase wee1; Tome-1 therefore appears to be acting as part of an SCF-type E3 for wee1. Degradation of Tome-1 during G1 allows for wee 1 accumulation during interphase, thereby providing a critical link between the APC and SCF pathways in regulation of cdk1/cyclin B activity and thus mitotic entry and exit.
Insights
We identified Tome-1, a protein crucial for initiating mitosis by regulating CDK1/cyclin B activity. Its degradation in G1 links the APC and SCF pathways, controlling cell cycle progression.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mitotic entry and exit are tightly regulated by the cell cycle.
- Cyclin B degradation, mediated by the anaphase-promoting complex (APC), is critical for mitotic exit.
- The precise mechanisms linking APC activity to mitotic entry require further elucidation.
Purpose of the Study:
- To identify novel substrates of the APC.
- To elucidate the role of a newly identified APC substrate, Tome-1, in regulating cell cycle progression.
- To understand the interplay between APC and SCF pathways in controlling CDK1/cyclin B activity.
Main Methods:
- Protein identification and characterization.
- Yeast two-hybrid screening to identify interacting partners.
- Western blotting to assess protein degradation and accumulation.
- Cell cycle analysis to determine effects on mitotic entry.
Main Results:
- A novel APC substrate, Tome-1 (trigger of mitotic entry), was identified.
- Tome-1 is a cytosolic protein essential for CDK1/cyclin B activation and mitotic entry.
- Tome-1 interacts with Skp-1 and mediates the degradation of wee1, a CDK1 inhibitor.
- Tome-1 degradation during G1 allows wee1 accumulation, linking APC and SCF pathways.
Conclusions:
- Tome-1 acts as a critical link between the APC and SCF ubiquitin ligase pathways.
- Regulation of Tome-1 stability by the APC is essential for controlling CDK1/cyclin B activity.
- This regulatory axis ensures proper mitotic entry and exit, maintaining cell cycle fidelity.
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