The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1.
By Cathie M Pfleger, Marc Kirschner. Genes & Development, 2000
800 citations recorded by the source corpus.
The ordered progression through the cell cycle depends on regulating the abundance of several proteins through ubiquitin-mediated proteolysis. Degradation is precisely timed and specific. One key component of the degradation system, the anaphase promoting complex (APC), is a ubiquitin protein ligase. It is activated both during mitosis and late in mitosis/G(1), by the WD repeat proteins Cdc20 and Cdh1, respectively. These activators target distinct sets of substrates. Cdc20-APC requires a well-defined destruction box (D box), whereas Cdh1-APC confers a different and as yet unidentified specificity. We have determined the sequence specificity for Cdh1-APC using two assays, ubiquitination in a completely defined and purified system and degradation promoted by Cdh1-APC in Xenopus extracts. Cdc20 is itself a Cdh1-APC substrate. Vertebrate Cdc20 lacks a D box and therefore is recognized by Cdh1-APC through a different sequence. By analysis of Cdc20 as a substrate, we have identified a new recognition signal. This signal, composed of K-E-N, serves as a general targeting signal for Cdh1-APC. Like the D box, it is transposable to other proteins. Using the KEN box as a template, we have identified cell cycle genes Nek2 and B99 as additional Cdh1-APC substrates. Mutation in the KEN box stabilizes all three proteins against ubiquitination and degradation.
Subfields: Cell Biology, Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/b974c20d34ae0abfc35669757ff918b2665d1d85
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Citations in the corpus
- Global Subcellular Characterization of Protein Degradation Using Quantitative Proteomics (2012, neutral): “Many of these novel RDPs contain known degradation targeting motifs, such as Anaphase Promoting Complex (APC/C) KEN-boxes (32, 33), APC/C D-boxes (33, 34), and Skp1-Cullin-Fbox (SCF) FBXW7-binding sites (35, 36) (supplemental Table S3).”
- Understanding eukaryotic linear motifs and their role in cell signaling and regulation. (2008, background): “These criteria have been applied in a survey of KEN box candidates (64).”
- The eukaryotic linear motif resource ELM: 10 years and counting (2013, background): “Destruction of substrate proteins is facilitated by interactions with the bound co-activators, also mediated via short linear motifs (called degradation motifs or degrons), such as the well-characterized D-Box (33) and KEN-Box motifs (34,35).”