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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
Ubiquitination site preferences in anaphase promoting complex/cyclosome (APC/C) substrates
Mingwei Min1, Ugo Mayor, Catherine Lindon
1Department of Genetics, University of Cambridge, Downing Street, Cambridge CB2 3EH, UK.
Open Biology
|September 6, 2013
Summary
The anaphase promoting complex/cyclosome (APC/C) targets substrates for destruction during mitosis. This study reveals KEN motifs are preferred ubiquitination sites, regulated by phosphorylation near serine residues, adding a new layer to cell cycle control.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Mitotic progression relies on precise regulation of key protein abundance.
- The anaphase promoting complex/cyclosome (APC/C) is a ubiquitin ligase crucial for degrading mitotic regulators.
- APC/C substrate specificity is primarily linked to D-box and KEN degrons, but ubiquitination site specificity remains unexplored.
Purpose of the Study:
- To investigate the specificity of ubiquitination sites in APC/C substrates.
- To explore the role of KEN motifs as ubiquitin acceptors.
- To understand how phosphorylation influences APC/C-mediated substrate degradation.
Main Methods:
- Analysis of the APC/C substrate ubiquitome.
- Experimental validation of KEN lysine as a ubiquitin acceptor site.
- Investigating the impact of phosphorylation on serine residues flanking KEN motifs using Aurora A and Nek2 kinases.
Main Results:
- The KEN motif is identified as a preferred ubiquitin acceptor site on APC/C substrates.
- Ubiquitination acceptor sites are frequently located in disordered regions and adjacent to serine residues.
- Phosphorylation of serine residues near KEN motifs directly regulates ubiquitination and subsequent substrate degradation.
Conclusions:
- A novel regulatory mechanism for APC/C-mediated substrate targeting is proposed, involving phosphorylation adjacent to the KEN motif.
- This phosphorylation event fine-tunes substrate ubiquitination and degradation, contributing to precise mitotic control.
- Understanding this regulatory layer enhances our knowledge of cell cycle progression and protein turnover.
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