Two Israelis and an American won the Nobel Prize in Chemistry yesterday for discovering the method by which cells tag proteins that are defective or have outlived their usefulness and direct them to the cellular machinery that grinds them up into reusable parts.

This system not only recycles raw materials, it regulates many of a cell's activities by removing specific actors -- the "target" proteins -- from the stage during important scenes in the cell's life. The key molecule involved -- ubiquitin -- is so useful it exists in nearly identical form in yeast and human beings -- and in every organism between them on the evolutionary ladder.

The Royal Swedish Academy of Sciences gave the award to Irwin Rose, 78, of the University of California at Irvine and Avram Hershko, 67, and Aaron Ciechanover, 57, both of the Israel Institute of Technology in Haifa "for the discovery of ubiquitin-mediated protein degradation." The three will share $1.36 million.

The ubiquitin pathway's potential importance in medicine is only now emerging, a quarter-century after the trio's discoveries.

A few rare diseases are caused by defects in the enzymes that help attach ubiquitin to its protein target, or that detach it when its work is done. One drug that works in the ubiquitin pathway is in clinical use -- bortezomib, sold as Velcade, a medicine for the blood cancer multiple myeloma.

What the three scientists found "started out as a simple biochemical curiosity," said Keith D. Wilkinson, a biochemist at Emory University and an expert on the subject. "It has turned out to be of profound importance in understanding the regulation of the cell."

The name ubiquitin is derived from the Latin word for "everywhere." The molecule, itself a protein made of 76 linked building blocks called amino acids, turns out to have a role in myriad cellular functions. They include regulating the "cell cycle," or steps of division; repairing the genetic material, DNA; modulating receptors that pick up signals from the outside environment; and fine-tuning certain aspects of immunity.

What all those activities share is ubiquitin's ability to be attached firmly, but temporarily, to a protein that has been identified as needing some sort of work done on it.

That attachment -- through a covalent bond -- allows the protein to be manipulated or transported with greater precision and efficiency than if the cell relied on weaker forms of attraction.

Rose and Hershko met at a scientific meeting at the National Institutes of Health in 1976. Hershko asked the older scientist what problems interested him, and Rose answered "protein degradation" -- exactly Hershko's research focus.

"I asked him, 'Why do I never see anything published by you on this subject?' " Hershko recalled yesterday. "He answered, 'Because I don't have anything worth publishing.' I liked his attitude. He has very rigorous criteria, and as you can tell, he was quite a character."

Both men were interested in understanding why the act of breaking down proteins required energy -- consumption of the molecule ATP, the cell's basic unit of fuel -- just as the construction of proteins required energy.

Rose, Hershko and Ciechanover, one of Hershko's graduate students, worked on the problem separately, as well as over several summers and sabbaticals the Israelis spent at Rose's laboratory at the Fox Chase Cancer Center in Philadelphia.

They learned that the energy is spent attaching ubiquitin to target proteins, with the help of a trio of enzymes, called E1, E2 and E3. (The E3s are in many ways the most interesting of these assistants. There are genes encoding 500 different E3s in the human genome, each one identifying members of a different protein family.)

When a protein is slated for removal, a long string of ubiquitin molecules attaches to it before the whole assembly is taken to a barrel-like structure in the cell's interior called a proteasome. The protein is stuffed into the barrel, where it is broken down into individual amino acids. The ubiquitins are clipped off and sent back to work.

Scientists now know that ubiquitin is sometimes attached to proteins -- singly, not in multiples -- for purposes other than directing them into the recycler. The molecule's full uses are still being discovered.

Bacteria do not use ubiquitin. But all cells with a nucleus -- called eukaryotes -- do. It appears to be the gene among the 30,000 human beings possess that has changed least during the course of evolution. Our ubiquitin differs from that of yeast by only 3 amino acids in the molecule's 76-amino-acid structure.

Rose moved to California after retiring from Fox Chase, where he worked for 34 years. He now does research on other subjects at a lab at UC-Irvine. He was woken yesterday by a telephone call from Sweden at 2 a.m. but managed to go back to sleep until 8:30, when someone from the university press office knocked on his door.

"I feel kind of numb. It's not my routine feeling," he said yesterday.

Yesterday was a holiday in Israel, for Sukkot, the harvest festival. Hershko got his news at a swimming club when a cousin called his cell phone and told him what he had heard on the radio.

Hershko said he explained what the Nobel Prize was to his four young granddaughters, who were with him. They were most interested in what they would wear to the award ceremony in Stockholm in December.

"I told them, 'You have to wear a white dress because you meet the king and queen.' They were very impressed by this," he said. He added he plans to bring all six of his grandchildren to Sweden.

Ciechanover, his colleague at Technion, the other name for the Israeli institute, could not be reached.