Avram Hershko is a Distinguished Professor at the Technion—Israel Institute of Technology who shared the 2004 Nobel Prize in Chemistry with Aaron Ciechanover and Irwin Rose for the discovery of ubiquitin-mediated protein degradation. Hershko's contributions were central to working out the biochemical mechanism by which proteins are tagged with the small protein ubiquitin and subsequently destroyed by the 26S proteasome. His laboratory characterized the key enzymatic players in this process, including the ubiquitin-activating enzyme (E1) and the ubiquitin-conjugating enzymes (E2s), establishing the stepwise cascade that marks proteins for degradation. This work has been fundamental to understanding cell cycle regulation, as many cyclin proteins are degraded via the UPS. The cell cycle implications of his work have had direct consequences for cancer drug development; multiple anti-cancer agents targeting cell cycle regulators exploit the UPS. Hershko's research also illuminated how the UPS contributes to antigen presentation in the immune system, informing immunotherapy strategies.