Fig. 1.

The Skp1, Cullin, F-box protein (SCF) E3 ligase-mediated ubiquitin-proteasome system of protein degradation. Ubiquitin (Ub) is conjugated to substrate proteins through effort of three enzymes by an ATP-dependent process. First, ubiquitin is activated by an ubiquitin-actvating enzyme (E1) in an ATP-dependent way and transferred to its active site through formation of a thiol-ester bond between the ubiquitin and E1. Then the ubiquitin is passed to the second enzyme complex, the ubiquitin-conjugating enzyme (E2), through the same thiol-ester linkage. Finally, the target substrate is recognized by the third enzyme complex, ubiquitin ligase (E3), and labeled with the ubiquitin. This process can be repeated and a multiubiquitin chain can be formed, which usually targets the substrate for proteolysis by the 26S proteasome.