Aaron Ciechanover

Aaron Ciechanover, with Avram Hershko at the Technion and Irwin Rose at the Fox Chase Cancer Center, discovered ubiquitin-mediated protein degradation: the cell tags a protein with a chain of ubiquitin molecules and the proteasome then destroys it. The three shared the 2004 Nobel Prize in Chemistry, one third each, "for the discovery of ubiquitin-mediated protein degradation". The clinical consequences are direct. Blocking the proteasome kills myeloma cells, which is what bortezomib and carfilzomib do. Redirecting the tagging machinery at a protein of choice is what PROTACs and molecular glues do, and it is how drugs are now being made against targets long called undruggable. Ciechanover continues to publish from the Rappaport-Technion Integrated Cancer Center on the ubiquitin-proteasome system in cancer and on degrader technology in myeloma and lymphoma.