Fig. 1

The ubiquitination and deubiquitination cycle. The ubiquitination process is conducted by three key enzymes that function sequentially. The ubiquitin-activating enzyme E1 promotes the formation of a thioester bond between the C-terminal carboxyl group of ubiquitin and the E1 cysteine sulfhydryl group in an ATP-dependent manner. Then ubiquitin is transferred from E1 to the active site of conjugating enzyme E2. Finally, the E3 ubiquitin ligase catalyzes the attachment of ubiquitin to the substrate through an isopeptide bond between the lysine of the target protein and the glycine of ubiquitin. The E3 enzymes are central in this cycle due to their ability to determine the specificity of the ubiquitination process via discriminating various substrates in cells. On the contrary, the deubiquitinases (DUBs) release the ubiquitin linked with substrates to regulate the stability and function of targeted proteins and the ubiquitin can be utilized in circulation