The discoverers of a system for disposing of proteins inside cells have been awarded this year's Nobel Prize in chemistry. Aaron Ciechanover and Avram Hershko of the Rappaport Institute at the Technion-Israel Institute of Technology in Haifa and Irwin Rose of the University of California, Irvine, share this year's prize for work that established how a protein called ubiquitin tags other proteins for recycling.
While most biochemists in the 1970s were studying how the cell makes proteins, Hershko got interested in a less-studied puzzle: why the cell requires energy to break down proteins. In 1979, he and Ciechanover, then a postdoctoral student, did a series of experiments while visiting Rose's lab at the Fox Chase Cancer Center in Philadelphia. The experiments showed that proteins destined for destruction were covalently bonded--a process that requires energy--to a small protein they called APF-1. That protein later turned out to be ubiquitin, which had been identified by other researchers a few years earlier.
The three went on to show that three additional proteins work with ubiquitin to tag the proper proteins for disassembly. They and others subsequently showed that ubiquitin then delivers the doomed proteins to the proteasome, a large complex that breaks down the chemical bonds holding proteins together and releases the amino acid building blocks for reuse. Ciechanover says the discoveries helped to explain how the protein-degrading proteasome can coexist with proteins in the cell's cytoplasm without breaking down the wrong ones. "The shark and the bait are living together peacefully, and they will interact only following the tag from ubiquitin," he says.
Ubiquitin also has since been shown to play a role in the cell's proofreading of newly made proteins, as well as in cell division, DNA repair, the immune system, and cystic fibrosis. Kim Nasmyth of the Research Institute of Molecular Pathology in Vienna, who helped clarify the role of ubiquitin in cell division, calls the experiments "an extraordinary tour de force of classical biochemistry" and says the prize is well-deserved. "This is a discovery that has impacted on every single branch of biology and is a beautiful bit of chemistry," he says.