In October 2004, the Royal Swedish Academy of Sciences awarded the Nobel Prize in Chemistry to Aaron Ciechanover, Avram Hersko, and Irwin Rose "for the discovery of ubiquitin-mediated protein degradation." Their seminal work in the 1970s and 1980s opened the door for the next generation of "ubiquitinologists," including Alexander Varshavsky, Keith Wilkinson, and Arthur Haas, who discovered that ubiquitin (8 kDa), a highly conserved protein, becomes covalently attached to lysine residues of target proteins (ubiquitination). The researchers subsequently showed that this attachment occurs through a three-step process involving ubiquitin-activating (E1), ubiquitin-conjugating (E2), and ubiquitin-ligating (E3) enzymes.