Maintenance of cellular function requires timely and selective degradation of key regulatory proteins. For example, progression of the mammalian cell cycle is regulated by the degradation of key cell cycle proteins via the ubiquitin pathway. Ubiquitin, a soluble protein of 76 amino acids, is enzymatically attached to an ε-NH2-Lys in a target protein. Ubiquitin-conjugated proteins are recognized and degraded by the 26S proteasome. Targeting of specific cellular proteins for degradation via the ubiquitylation pathway may require the formation of protein complexes. One group of ubiquitin enzyme containing complexes are the multisubunit cullin-containing RING E3 ubiquitin ligases, that include SCF and VCB-Cul-2 complexes. These complexes contain a RING domain protein, a cullin, multiple adaptor proteins, and ubiquitin enzymes. The SCF complex includes Skp1, SGT1, Cul-1, F-box protein, and CDC34/Ubc3. This complex preferentially ubiquitylates phosphoproteins, such as β-catenin, IκBα, and G1 cyclins. The mammalian SGT1 is an adaptor protein that can interact with Skp1 and can rescue yeast SGT1 null mutations. Thus, SGT1 may be an important component of the SCF ubiquination ligase complex.