A UC Irvine researcher and two Israeli scientists Wednesday were awarded the 2004 Nobel Prize in chemistry for their discovery of the cellular system that, like a miniature Mafia don, gives the "kiss of death" to proteins marked for destruction.
The system was initially thought to be used only for getting rid of defective proteins or those that had outlived their usefulness to the cell, but 25 years of research have shown that it is intimately involved in a variety of processes that includes cellular replication, cystic fibrosis and other diseases, the immunological response and even cancer.
Irwin A. Rose, 78, an emeritus professor at UC Irvine, and Aaron Ciechanover, 56, and Avram Hershko, 70, of the Technion-Israel Institute of Technology in Haifa will share the $1.35-million prize. It is the first Nobel awarded to Israeli scientists and the third to a faculty member at UC Irvine.
The team's research "has given us an important close-up view of the regulatory processes taking place inside human cells and what happens when these processes don't work correctly," said Charles P. Casey of the University of Wisconsin-Madison, president of the American Chemical Society. It "provides a cornerstone for the development of new drugs" against cancer and other diseases.
One cancer drug based on inhibiting this system, Velcade, is already on the market, and several others for cancer and degenerative diseases are in development, experts said.
"The practical applications are too numerous to mention," Rose said.
The award is a case study for the benefits of going against the conventional wisdom.
When Rose and Hershko met at a conference in 1979, the majority of protein researchers were interested in tracing the mechanisms by which the 100,000 or so proteins in each individual cell were produced. In fact, five Nobel prizes have been presented for studies of those mechanisms.
Researchers knew that proteins had to be broken down in the cell, Rose said, but "nobody had a clue as to how it worked."
That chance meeting led to a decades-long collaboration between Rose and Hershko and, soon thereafter, Ciechanover, who was a graduate student in Hershko's lab in Israel.
Both Israelis took sabbaticals in Rose's lab at the Fox Chase Cancer Center in Philadelphia, and Hershko came to work in the lab virtually every summer for 19 years.
