Ubiquitin-directed degradation by the 26S proteasome is central to the control and regulation of a multitude of cellular processes.
The covalent attachment of polyubiquitin chains to target proteins is coordinated by three classes of enzymes: E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme, and E3 ubiquitin ligase. E1 is responsible for activating ubiquitin and passing it on to E2. E2 then assembles with E3 and transfers ubiquitin to a substrate protein. Multiple rounds of ubiquitin transfer occur to form polyubiquitin chains on the target protein and flag it for destruction. The E3 ligases play a critical role in this process because they determine the substrate specificity of the ubiquitination reaction. The two major types of E3 ligases are the cullin-RING-finger ligases (CRLs) and the anaphase-promoting complex/cyclosome (APC/C). The core complex of CRLs is composed of a cullin-homology domain-containing protein, a RING-H2 protein, and an adapter protein which facilitates interaction with substrate receptors. Seven cullin proteins have been identified in vertebrates: Cul1, Cul2, Cul3, Cul4a, Cul4b, Cul5, and Cul7. Studies indicate that each cullin protein associates with specific bridging adaptors and substrate receptors in the core complex to form substrate specific ligases. For example Cul1 associates with Skp1 and an F-box protein to form the SCF (Skp1, Cul1, F-box) ligase. In this complex, Skp1 bridges Cul1 to the F-box protein which functions as the substrate specific adaptor. Other Cul-based ligases include ECS (Elongin C, Cul2, SOCS), Cul4-DDB (DDB, Cul4, DCAF) and Cul3-BTB. A multitude of F-box, SOCS, BTB-domain, and DCAF factors have been identified and provide a critical means for assigning substrate specific activity to the E3 ligase function.
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2. J. Lee and P. Zhou, "DCAFs, the Missing Link of the CUL4-DDB1 Ubiquitin Ligase," Mol Cell. 26, no. 6 (2007): 775-780.
3. L. Pintard, A. Willems, and M. Peter, "Cullin-Based Ubiquitin Ligases: Cul3-BTB Complexes Join the Family," EMBO J. 23, no. 8 (2004): 1681-1687.
Bethyl Laboratories Portfolio of Cullin E3 Ligase Antibodies
Rabbit Monoclonal Cullin Antibodies from Epitomics ...