Skp2 contains 424 residues in total with the approximate 40 amino acid F-box domain lying closer to the N-terminal region at the 94-140 position and the C-terminal region forming a concave surface consisting of ten leucine-rich repeats (LRRs). The F-box proteins constitute one of the four subunits of ubiquitin protein ligase complex called SCFs. In this SCF complex, Skp2 acts as the substrate recognition factor. Skp2 forms a stable complex with the cyclin A-CDK2 S-phase kinase. It specifically recognizes and promotes the degradation of phosphorylated cyclin-dependent kinase inhibitor 1B predominantly in S, G2 phase, and the initial part of the M phase. Overexpression of Skp2 results in increased CDK activity and contributes to the deregulated proliferation and genetic instabilities typical of cancer cells.
