E3 Ligases of the Ubiquitin Protease System

The ubiquitin protease system involves a four-step enzyme cascade, which incorporates at least three enzymatic activities. The E1 ubiquitin-activating enzyme plays a role in the first step of the pathway and is responsible for delivering activated ubiquitin to the reaction. The E2 ubiquitin-conjugating enzyme receives the activated ubiquitin and transfers it to the target protein. Transfer of ubiquitin to the target is facilitated by the E3 ligase. The E3 ligase is responsible for dictating substrate specificity and bridging the activity of the ubiquitin-conjugating E2 enzyme with its target. The E3 ligases are a large and diverse group of proteins that exists as multi-protein complexes or as single proteins. E3 enzymes can be classified into at least 3 groups based on their structural domains. These domains include the HECT (homologous to E6-associated protein C-terminus), RING (really interesting new gene), or U-box (a modified RING motif without the full complement of Zn2+-binding ligands) domain. Because E3 ligases dictate target specificity, this group of enzymes is being considered as a target in the treatment of human diseases caused by defects in the ubiquitin protease system.

Selected Reviews

1. Lee J, and Zhou P. 2010. Cullins and Cancer. Genes Cancer 1 (7): 690-699.

2. Robinson PA, and Ardley HC. 2004. Ubiquitin-protein ligases. J. Cell Sci. 117 (Pt 22): 5191-5194.

3. Scheffner M, and Staub O. 2007. HECT E3s and human disease. BMC. Biochem. 8 Suppl 1: S6.

E3 Ligase Product Portfolio

APC1, APC4, APC5, APC7, BARD1, BMI1, BRCA1, BRCC36, CAND1, Cbl-b, CBX8, c-Cbl, CDC16/APC6, CDC23/APC8, COP1/RFWD2, Cul2, Cul3, Cul4a, Cul5, Cul7, DDB1, DTL/CDT2, DTX3L/BBAP, E4F1, EDD1, FBW7, FBXO11, FBXO31, FLRF/RNF41, Hakai, HECTD1, HERC1, HERC2, HERC4, Itch, Lasu1/Ureb1, MGRN1, MIB2/Skeletrophin, MKRN1, MKRN2, NEDD4L, NP95/UHRF1, NRIP, p600, PAM, PARC/H7-AP1, Rad18, RFWD3, Synoviolin, TOPORS, Triad1, TRIM33/TIF1gamma, TRIM37, TRIM41, TRIP12, ZNRF2.