Ubiquitination: Proteins destined for degradation are tagged with ubiquitin molecules in a process catalyzed by three enzymes: E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin ligase). Recognition and Binding: The ubiquitinated proteins are recognized and bound by the 19S regulatory particle of the proteasome. Degradation: The proteins are unfolded and translocated into the 20S core particle of the proteasome, where they are cleaved into small peptides.