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Dimerization regulates the human APC/C-associated ubiquitin-conjugating enzyme UBE2S
Anna K L Liess1, Alena Kucerova2, Kristian Schweimer3
1Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, 97080 Würzburg, Germany.
Science Signaling
|October 21, 2020
Summary
Ubiquitin-conjugating enzymes (E2s) regulate protein ubiquitination. UBE2S dimerization inhibits its activity, preventing rapid turnover and ensuring cell cycle control during mitosis.
Area of Science:
- Biochemistry
- Cell Biology
- Molecular Biology
Background:
- Protein ubiquitination is a key cellular process regulated by ubiquitin-conjugating enzymes (E2s).
- Dysregulation of E2 enzymes is linked to cancer development.
- E2s can regulate their own stability through autoubiquitination.
Purpose of the Study:
- To investigate the regulatory mechanisms balancing E2 enzyme activity and stability.
- To understand the role of UBE2S, an APC/C-associated E2, in cell cycle regulation.
Main Methods:
- Dissection of UBE2S regulatory dynamics.
- Analysis of UBE2S dimerization and its impact on catalytic activity.
- Assessment of dimerization-deficient UBE2S in cellular turnover and mitotic arrest models.
Main Results:
- UBE2S exists in a dimeric state that inhibits its catalytic activity by blocking a ubiquitin binding site.
- Dimerization is promoted by a carboxyl-terminal extension, which also mediates APC/C recruitment and autoubiquitination.
- Dimerization-deficient UBE2S exhibits increased turnover and impaired mitotic regulation.
Conclusions:
- Dimerization of UBE2S attenuates its autoubiquitination-induced turnover when the APC/C is less active.
- Mutually exclusive macromolecular interfaces modulate E2 enzyme activity and abundance for precise ubiquitin signaling.
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