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Published on: October 11, 2022
Transcriptional and post-transcriptional regulation of Cdc20 during the spindle assembly checkpoint in S. cerevisiae
Ruiwen Wang1, Janet L Burton2, Mark J Solomon2
1Institute of Life Sciences, College of Biological Science and Engineering, Fuzhou University, Fuzhou, Fujian Province 350108, China.
Abstract:
The anaphase-promoting complex (APC) is a ubiquitin ligase responsible for promoting the degradation of many cell cycle regulators. One of the activators and substrate-binding proteins for the APC is Cdc20. It has been shown previously that Cdc20 can promote its own degradation by the APC in normal cycling cells mainly through a cis-degradation mode (i.e. via an intramolecular mechanism). However, how Cdc20 is degraded during the spindle assembly checkpoint (SAC) is still not fully clear. In this study, we used a dual-Cdc20 system to investigate this issue and found that the cis-degradation mode is also the major pathway responsible for Cdc20 degradation during the SAC. In addition, we found that there is an inverse relationship between APCCdc20 activity and the transcriptional activity of the CDC20 promoter, which likely occurs through feedback regulation by APCCdc20 substrates, such as the cyclins Clb2 and Clb5. These findings contribute to our understanding of how the inhibition of APCCdc20 activity and enhanced Cdc20 degradation are required for proper spindle checkpoint arrest.
Insights
The anaphase-promoting complex (APC), a key cell cycle regulator, degrades Cdc20 via cis-degradation during the spindle assembly checkpoint (SAC). This process, along with feedback regulation, ensures proper cell cycle arrest.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The anaphase-promoting complex (APC) is a crucial ubiquitin ligase regulating the cell cycle.
- Cdc20 acts as an activator and substrate-binding protein for the APC.
- Cdc20 degradation via APC in normal cycling cells primarily occurs through cis-degradation.
Purpose of the Study:
- To elucidate the degradation mechanism of Cdc20 during the spindle assembly checkpoint (SAC).
- To investigate the role of cis-degradation in Cdc20 turnover during SAC.
- To explore the relationship between APCCdc20 activity and CDC20 gene transcription.
Main Methods:
- Utilized a dual-Cdc20 system to study Cdc20 degradation.
- Investigated the mechanism of Cdc20 degradation during the spindle assembly checkpoint.
- Analyzed the transcriptional activity of the CDC20 promoter in relation to APCCdc20 activity.
Main Results:
- Cis-degradation is identified as the major pathway for Cdc20 degradation during the spindle assembly checkpoint (SAC).
- An inverse relationship was observed between APCCdc20 activity and CDC20 promoter transcriptional activity.
- Feedback regulation by APCCdc20 substrates, including cyclins Clb2 and Clb5, likely mediates this inverse relationship.
Conclusions:
- Cdc20 degradation during SAC predominantly occurs via cis-degradation.
- Feedback regulation mechanisms involving APCCdc20 substrates modulate CDC20 transcription.
- These findings highlight the importance of APCCdc20 inhibition and Cdc20 degradation for effective spindle checkpoint arrest.
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