- Person
- Irwin Rose
- Lived
- 1926–2015
- Field
- Biochemistry
- From
- American
The story
By the 1970s biologists understood a great deal about how cells build proteins but very little about how they get rid of them. Experiments going back to the 1950s showed something puzzling: the breakdown of the cell’s own proteins required energy, while the digestion of proteins in food did not. Irwin Rose, an enzyme chemist at the Fox Chase Cancer Center in Philadelphia, had first read about this paradox during his first year at Yale in the 1950s and kept working on it on the side for some twenty years.
In the late 1970s the Israeli biochemists Avram Hershko and Aaron Ciechanover of the Technion began spending sabbaticals in Rose’s laboratory. They had found that a small, heat-stable protein, which they called APF-1, was essential for energy-dependent protein breakdown in extracts of immature red blood cells. In 1979 Rose asked his institute’s director for nearly $50,000 to extend their stay to a full year. In two papers in 1980 the three showed that APF-1 attaches firmly to proteins that are about to be destroyed, and that many copies can be strung onto the same target. APF-1 turned out to be ubiquitin, a protein found in nearly every cell; a postdoctoral fellow in Rose’s laboratory, Keith Wilkinson, was the first to identify it as such.
Between 1981 and 1983 the team worked out the machinery. One enzyme uses energy to activate ubiquitin, a second carries it, and a third recognises the specific protein to be removed and attaches the chain. The chain sends the protein to the proteasome, the cell’s waste disposer, which chops it into small pieces. The Nobel committee called the label a kiss of death.
The system turned out to control cell division, DNA repair, quality control of new proteins and parts of the immune response, and its failures play a part in some cancers and in cystic fibrosis. The proteasome inhibitor bortezomib (Velcade), approved in the United States in 2003, became a standard treatment for multiple myeloma and later mantle cell lymphoma. Rose, Hershko and Ciechanover shared the 2004 Nobel Prize in Chemistry.
Why it matters
Drugs that block the cell’s ubiquitin-proteasome system, starting with bortezomib, now treat multiple myeloma and other blood cancers, and researchers are designing new medicines that use the ubiquitin tag to destroy disease-causing proteins.
About Irwin Rose
Brooklyn-born biochemist who helped discover how cells tag unwanted proteins with ubiquitin for destruction, knowledge behind myeloma drugs such as bortezomib. Nobel Prize 2004.
Sources
- The Nobel Prize in Chemistry 2004, Popular information NobelPrize.org
- Irwin Rose, Biographical NobelPrize.org
- Irwin Rose, 88; Nobel-winning biochemist The Boston Globe
- Bortezomib Wikipedia
Another act of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.