Daniel J. Finley
Harvard Medical School
Cellular and Developmental Biology
With his mentor Varshavsky, Daniel Finley discovered that the ubiquitin-proteasome system is the major mediator of eukaryotic protein degradation, revealing the role of ubiquitylation in cell cycle control. He also identified the first degradation signals in short-lived proteins, including the N-end rule, and showed that ubiquitylation was critical for stress responses. Subsequently, he discovered topologically variant polyubiquitin chains, specific chaperone proteins that are needed to assemble the proteasome's base, and obtained major insights into their mechanism. In addition, he discovered small-molecule inhibitors of one such factor, the Usp14deubiquitinating enzyme, achieving a specific enhancement of proteasome function in vivo.