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Protein "kiss of death" system gets Nobel


The body's quality control system for proteins is essential for getting rid of proteins that lead to errors in cell replication or genetic coding (Image: U.S. Department of Energy Human Genome Program)

Two Israeli and one U.S. scientist won the 2004 Nobel prize for chemistry this week for discovering the human body's method of getting rid of rogue proteins that ultimately lead to diseases like cancer.

Professors Aaron Ciechanover and Avram Hershko of the Technion Israel Institute of Technology in Haifa and Dr Irwin Rose University of California, Irvine won the prize for work in the 1980s that could help treat illnesses like leukemia and cystic fibrosis by identifying how the body "degrades" unwanted proteins.

"When the degradation does not work correctly, we fall ill. Cervical cancer and cystic fibrosis are two examples," the Royal Swedish Academy of Sciences said in its citation, adding that such knowledge "offers an opportunity to develop drugs against these diseases and others".

The scientists found that the unwanted proteins which could, for example, lead to errors in cell replication or genetic coding are "labelled" for destruction with a molecule called ubiquitin. It sends them to "waste disposal" units, called proteasomes, where they are chopped into small pieces.

"We are not a building that stays still, we are all the time exchanging our proteins, synthesising and destroying them," said an elated Ciechanover. "Some proteins get spoilt. We discovered the process by which the body exercises quality control."

Professor Lars Thelander of the Nobel Committee for Chemistry said the trio's work was highly relevant for cancer research.

Ciechanover said it had already "led to development of numerous drugs for degenerative diseases and malignancies that big pharmaceutical companies are busy working on".

One drug based on the research is the bone marrow cancer drug Velcade made by Millennium Pharmaceuticals.

Unwanted proteins that lead to errors in cell replication or genetic coding can lead to malignant tumours or cause Down's syndrome or miscarriage.

Molecular cell biologist Professor John Mayer at Nottingham University said the role of protein breakdown in such processes was "absolutely fundamental".

"There is nothing in the cell that can work without some role of ubiquitin or its cousins," he said, adding the laureates' research had "enormous" significance for understanding the human immune system and fighting diseases such as cancers and neurological illnesses.

Ciechanover, Hershko and Rose will share the 10 million Swedish crown (US$1.36 million) prize. Ciechanover said it would be a welcome boost in income for the low-paid Israeli researchers - and for Israeli science.

"I have never thought of money, we earn very small salaries in Israel," he said. "It is more the honour for Israel, for myself, that a small country can make it."

Rose gave Hungarian-born Hershko much of the credit: "There's no question about it that he did the major work in this field. I was a contributor and I never felt I was really the key person."

Tags: health, biology, chemistry, computers-and-technology