The attachment of ubiquitin and ubiquitin-like polypeptides to intracellular proteins is a key mechanism in regulating many cellular and organismal processes. Assembly of a chain of at least four ubiquitins linked together via their Lys48 residue marks cellular proteins for degradation by the 26S proteasome. In contrast, monoubiquitination or polyubiquitination with chains linked together via Lys63 serve as nonproteolytic signals in intracellular trafficking, DNA repair, and signal transduction pathways. Ubiquitination of proteins is achieved through an enzymatic cascade involving ubiquitin-activating (E1), ubiquitin-conjugating (E2), and ubiquitin-ligating (E3) enzymes (EC 6.3.2.19). Two major types of E3s exist in eukaryotes, defined by the presence of either a HECT or a RING domain[1]. The SCF (Skp1, Cullins, F-box proteins) multisubunit E3 ubiquitin ligase, also known as CRL (Cullin-RING ubiquitin Ligase) is the largest E3 ubiquitin ligase family that promotes the ubiquitination of various regulatory proteins for targeted degradation, thus regulating many biological processes, including cell cycle progression, signal transduction, and DNA replication[2].