Fig. 1.

The ubiquitin-dependent and ubiquitin-independent proteolysis. (a) The ubiquitin-dependent proteolysis is a three-step process that requires the presence of ubiquitin molecules and ATP consumption. E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating enzyme and E3 ubiquitin ligase enzyme are responsible for tagging the protein substrate with ubiquitin molecules. This process is repeated to generate a poly-ubiquitin chain, the standard form of which is tetra-ubiquitin. The ubiquitinated protein is recognized, unfolded and degraded by the 26S proteasome after the deubiquitinating enzymes (DUBs) remove the ubiquitin molecules from the protein substrate. The released free ubiquitin molecules will be used in another ubiquitination cycle. (b) Oxidatively modified proteins and partially or loosely unfolded proteins are degraded mainly by the 20S proteasome in a ubiquitin/ATP-independent manner.