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3 biochemists will share Nobel

Their work revealed the hidden disposal machinery of cells

Aaron Ciechanover; Avram Hershko; Irwin Rose
Aaron Ciechanover; Avram Hershko; Irwin Rose

Three biochemists — two Israelis and one American — have received the 2004 Nobel Prize in chemistry for uncovering the hidden disposal machinery inside every cell.

Announced Wednesday by the Royal Swedish Academy of Sciences, chemistry's highest honor goes to Aaron Ciechanover, 57, and Avram Hershko, 67, both of Technion (Israel Institute of Technology in Haifa); and Irwin Rose, 78, of the University of California-Irvine. They will split the $1.36 million prize equally.

They "have made it possible to understand at a molecular level how the cell controls a number of very important biochemical processes," says the Nobel citation.

In a series of papers published in the 1970s and '80s, the three biochemists and their collaborators uncovered how the cells rid themselves of proteins — the hammer and nails of biological processes — once they are no longer needed. "Every aspect of a cell metabolism is affected by the proteins you have," Rose says.

Cells attach a protein marker called ubiquitin — the "kiss of death," in the award's words — to unwanted proteins, marking them for disposal in a cellular system of startling complexity, the scientists found. Mishaps in the disposal process are tied to diseases such as cystic fibrosis and some cancers.

"It isn't often you uncover something fundamental about cells that also points to new ways to treat diseases," says biochemist Cecile Pickart of Johns Hopkins University. The prize points to the underappreciated role of chemistry in biomedicine, she says.

Prior to these discoveries, biochemists had focused on how the cell manufactures proteins rather than how it destroys them. It was thought that most proteins degraded after use, "wearing out like cars," says biochemist Michele Pagano of New York University, where Hershko is an adjunct professor.

Instead, their discoveries revealed that cells tightly regulate protein effects via disposal. It's a three-step process that slaps ubiquitin onto a doomed protein, consigning it to dismemberment inside a cellular "garbage disposal" called the proteasome. The process is now a standard lesson in college biology because it helps control cell division, repair and death.

"People do research, the good ones, because they are interested, because they want to find answers," Rose said Wednesday.

"This is a classic example of how basic research on the chemical mechanism underlying a biological process reveals a pathway essential to life," says a statement from the National Institutes of Health.

Hershko "still works at the lab bench here every summer," Pagano says. "I called him this morning to congratulate him and he wanted to discuss some samples I had recently sent him."

Researchers are increasingly trying to find treatments for diseases caused by malfunctions in the ubiquitin process involving flawed protein disposal. Last year, investigators began testing a proteasome inhibitor drug called Velcade in cancer patients, the first pharmaceutical treatment derived from the prize winners' discovery.