A hitchhiker's guide to the cullin ubiquitin ligases: SCF and its kin.
The SCF (Skp1-Cullin-F-box) E3 ubiquitin ligase family was discovered through genetic requirements for cell cycle progression in budding yeast. In these multisubunit enzymes, an invariant core complex, composed of the Skp1 linker protein, the Cdc53/Cul1 scaffold protein and the Rbx1/Roc1/Hrt1 RING domain protein, engages one of a suite of substrate adaptors called F-box proteins that in turn recruit substrates for ubiquitination by an associated E2 enzyme. The cullin-RING domain-adaptor architecture has diversified through evolution, such that in total many hundreds of distinct SCF and SCF-like complexes enable degradation of myriad substrates. Substrate recognition by adaptors often depends on posttranslational modification of the substrate, which thus places substrate stability under dynamic regulation by intracellular signaling events. SCF complexes control cell proliferation through degradation of critical regulators such as cyclins, CDK inhibitors and transcription factors. A plethora of other processes in development and disease are controlled by other SCF-like complexes, including those based on Cul2-SOCS-box adaptor protein and Cul3-BTB domain adaptor protein combinations. Recent structural insights into SCF-like complexes have begun to illuminate aspects of substrate recognition and catalytic reaction mechanisms.
Willems
Andrew R
AR
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Canada, M5G 1X5.
Schwab
Michael
M
Tyers
Mike
M
D000595:Amino Acid Sequence; D029681:Arabidopsis Proteins / Q000502:physiology; D044842:Cullin Proteins / Q000502:physiology*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D004718:Saccharomycetales / Q000201:enzymology / Q000502:physiology; D016415:Sequence Alignment; D025801:Ubiquitin / Q000502:physiology*; D014452:Ubiquitins / Q000502:physiology
D029681:Arabidopsis Proteins; C488785:CAND1 protein, Arabidopsis; D044842:Cullin Proteins; C513170:RUB1 protein, Arabidopsis; D025801:Ubiquitin; D014452:Ubiquitins