The SCF (Skp1-Cul1-F-box protein) complexes represent the largest family of ubiquitin-protein ligases and mediate the ubiquitination of a broad spectrum of regulatory and signalling proteins in diverse cellular pathways. The SCF consists of three invariant components, Skp1, Cul1 and Rbx1 and an interchangeable subunit, an F-box protein which is responsible for recruiting specific substrates to be ubiquitinated by the SCF. SCFSkp2 mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription. It specifically recognizes phosphorylated p27 and is involved in regulation of G1/S transition. Complex formation of SCFSkp2 with Cks1 is required for the degradation of p27. An increased level of Skp2 and reduced level of p27 is linked to poor prognosis in a number of cancers.