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- Title
Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication.
- Authors
Nash, P; Tang, X; Orlicky, S; Chen, Q; Gertler, F B; Mendenhall, M D; Sicheri, F; Pawson, T; Tyers, M
- Abstract
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.
- Publication
Nature, 2001, Vol 414, Issue 6863, p514
- ISSN
0028-0836
- Publication type
Journal Article
- DOI
10.1038/35107009