In eukaryotic cells, the major pathway for the selective degradation of cytosolic and nuclear proteins employs a molecule called ubiquitin. Ubiquitin is a 76-amino-acid polypeptide that is highly conserved in all eukaryotes. When attached in chains to proteins, ubiquitin targets the proteins for rapid proteolysis. A ubiquitin molecule is attached by its carboxy-terminal amino acid—which is a glycine—to the amino group of a lysine in the protein of interest. In turn, this first ubiquitin molecule