Regulation of the cell cycle is dependent on protein degradation by the ubiquitin-proteasome system. Two major ubiquitin ligases, the anaphase-promoting complex or cyclosome (APC/C) and SCF complex, are responsible for the periodic proteolysis of many regulators of the cell cycle. The receptor component of the SCF complex is one of many F-box proteins, three of which - Skp2, Fbw7, and β-TrCP - are well characterized and implicated in cell cycle regulation. We have generated mice deficient in Skp2, Fbw7, or β-TrCP1 and have identified the roles of these proteins in both cell cycle regulation and mouse development. Clinical evidence also suggests that dysregulation of these F-box proteins contributes to human cancers.
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