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Cullin-3 Targets Cyclin E For Ubiquitination And Controls S Phase In Mammalian Cells, Jeffrey D. Singer, Mark Gurian-West, Bruce Clurman, James M. Roberts
Cullin-3 Targets Cyclin E For Ubiquitination And Controls S Phase In Mammalian Cells, Jeffrey D. Singer, Mark Gurian-West, Bruce Clurman, James M. Roberts
Biology Faculty Publications and Presentations
Cyclin E is an unstable protein that is degraded in a ubiquitin- and proteasome- dependent pathway. Two factors stimulate cyclin E ubiquitination in vivo: when it is free of its CDK partner, and when it is phosphorylated on threonine 380. We pursued the first of these pathways by using a two-hybrid screen to identify proteins that could bind only to free cyclin E. This resulted in the isolation of human Cul-3, a member of the cullin family of E3 ubiquitin–protein ligases. We found that Cul-3 was bound to cyclin E but not to cyclin E-Cdk2 complexes in mammalian cells, and …