Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication.
SCF ubiquitin ligases target phosphorylated substrates for ubiquitin-dependent proteolysis by means of adapter subunits called F-box proteins. The F-box protein Cdc4 captures phosphorylated forms of the cyclin-dependent kinase inhibitor Sic1 for ubiquitination in late G1 phase, an event necessary for the onset of DNA replication. The WD40 repeat domain of ... Cdc4 binds with high affinity to a consensus phosphopeptide motif (the Cdc4 phospho-degron, CPD), yet Sic1 itself has many sub-optimal CPD motifs that act in concert to mediate Cdc4 binding. The weak CPD sites in Sic1 establish a phosphorylation threshold that delays degradation in vivo, and thereby establishes a minimal G1 phase period needed to ensure proper DNA replication. Multisite phosphorylation may be a more general mechanism to set thresholds in regulated protein-protein interactions.
Mesh Terms:
Binding Sites, Cell Cycle, Cell Cycle Proteins, Consensus Sequence, Cyclin-Dependent Kinase Inhibitor Proteins, DNA Replication, DNA, Fungal, Enzyme Inhibitors, F-Box Proteins, Fungal Proteins, Phosphorylation, Protein Structure, Tertiary, Saccharomyces cerevisiae Proteins, Substrate Specificity, Ubiquitin, Ubiquitin-Protein Ligases
Binding Sites, Cell Cycle, Cell Cycle Proteins, Consensus Sequence, Cyclin-Dependent Kinase Inhibitor Proteins, DNA Replication, DNA, Fungal, Enzyme Inhibitors, F-Box Proteins, Fungal Proteins, Phosphorylation, Protein Structure, Tertiary, Saccharomyces cerevisiae Proteins, Substrate Specificity, Ubiquitin, Ubiquitin-Protein Ligases
Nature
Date: Nov. 29, 2001
PubMed ID: 11734846
View in: Pubmed Google Scholar
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