Journal of Skin Cancer / 2011 / Article / Fig 1

Review Article

Tumor Suppressor Function of CYLD in Nonmelanoma Skin Cancer

Figure 1

Ubiquitin conjugation pathway. The ubiquitin pathway relies on a cascade of three enzymes, named ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin-ligating enzyme (E3), which conjugate ubiquitin to target proteins. First, ubiquitin is activated by the E1 enzyme in an ATP-dependent manner. As a consequence, ubiquitin is covalently bound to E1 via thioester bond with cysteine residue in the active site of the E1 enzyme. The ubiquitin is transferred to the active cysteine in E2 enzyme. Finally, with the help of an E3 enzyme, ubiquitin is conjugated to its target substrate where different ubiquitin-ubiquitin linkages help to decide the fate of the modified protein. Ubiquitination is primarily associated with degradation of the tagged protein by the 26S proteasome (Lys-48), but it has also nondegradative functions (Lys-63) such as the regulation of DNA repair and endocytosis amongst other functions. Enzymes known as deubiquitinating enzymes (DUBs) can remove ubiquitin from proteins.