CUL-1, which is the mammalian homolog of yeast Cdc53, is an integral component of the E3 ubiquitin ligase complex designated SCF. The SCF (Skp1/CUL-1/F-box protein complex) consists of Skp1 associating with both CUL-1 and an F-box protein, such as Skp2, which determines the substrate specificity of the complex. CUL-1-mediated ubiquitination results in the degradation of cell cycle proteins cyclin D, p21 and cyclin E. Another cullin, CUL-3, facilitates the degradation of cyclin E independent of SCF activity, while CUL-2 associates with the tumor suppressing protein VHL and elongin B to form VBC complexes, which structurally resemble the SCF ligase.