Ubiquitination is one of the most important post-translational modifications. There are usually three enzymes, E1, E2 and E3 (Scheffner et al., 1995), which mediate the process. E1, named 'ubiquitin-activating enzyme' (Haas et al., 1982), first activates ubiquitin, transfers it to its active site Cys. ATP is required as an energy source for the transfer (Ciechanover et al., 1980; Hershko et al., 1979). Secondly, E2, named 'ubiquitin-conjugating enzyme', binds E1 and conjugates the ubiquitin molecule from E1 to the site active Cys of E2 itself. The ubiquitin is then passed on to the target protein, via a final critical E3, named 'ubiquitin ligase', which recognizes the substrate and provides it with the ubiquitin (Deshaies et al., 2009). The substrate is attached with a polyubiquitin chain via repeats of the whole process and is finally taken to the proteasome for degradation