Three scientists were awarded the $1.35 million 2004 Nobel Prize for chemistry, thanks to their discovery that one particular component of the cellular system works a bit like a microscopic Mafia don, even marking cells for destruction in a process described as a kiss of death.
The three chemists, Irwin A. Rose, Aaron Ciechanover, and Avram Hershko will share the prize awarded for their collaborative discovery and continued study of the protein, ubiquitin, named for its ubiquitous presence in the human body, where it occurs in every cell. Rose now serves as an emeritus professor at the University of California, Irvine (UC Irvine), and Ciechanover and Herskho are both affiliated with the Technion-Israel Institute of Technology, Haifa.
A chance encounter at a 1979 conference led Rose and Hershko to embark on a collaborative study of the proteins, which number beyond 100,000, in each single cell. Ciechanover, one of Hershko’s graduate students, soon joined them.
While it was understood at that time that proteins in a cell had to be broken down for cellular regulation, the exact process was unknown in the 1970s although the topic was of great interest. Nineteen summer sabbaticals from Israel to Rose’s Philadelphia laboratory at the Fox Chase Cancer Center led to the discovery of ubiquitin.
On a cellular level, as many as 30% of all cellular proteins are defective, contributing to decay and disease within the cell if the defective proteins aren’t destroyed first. The Rose/Hershko/Ciechanover discovery showed the cell marking these defective proteins by attaching ubiquitin molecules to them, or marking with them with the cellular kiss of death, mentioned in the Nobel citation. Once marked, the proteins break down into smaller groups of amino acids, which the cell recycles for future use.
Although the research team seemed to be working against conventional wisdom from time to time, Hershko says the last ten years have seen an explosion of study on the subject. Current knowledge of the protein shows that it is directly involved in processes such as cellular replication, immunological response, cystic fibrosis, and cancer.
The cancer drug, Velcade, works by inhibiting the protein-marking process and is already being marketed, with several similar drugs under development for the treatment of cancer and other degenerative diseases.