作者
Piers Nash, Xiaojing Tang, Stephen Orlicky, Qinghua Chen, Frank B Gertler, Michael D Mendenhall, Frank Sicheri, Tony Pawson, Mike Tyers
发表日期
2001/11/29
期刊
Nature
卷号
414
期号
6863
页码范围
514-521
出版商
Nature Publishing Group UK
简介
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.
引用总数
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P Nash, X Tang, S Orlicky, Q Chen, FB Gertler… - Nature, 2001