- Person
- Aaron Ciechanover
- Lived
- b. 1947
- Field
- Biochemistry
- From
- Israeli
The story
Aaron Ciechanover was born in Haifa in 1947 to Jewish parents who had come from Poland in the 1920s, and was raised in a modern Orthodox home. Orphaned at sixteen, he trained as a doctor at the Hebrew University and Hadassah in Jerusalem, served as an army physician, and in 1976 began doctoral research with the biochemist Avram Hershko at the Technion in Haifa.
Scientists then knew a great deal about how cells build proteins but very little about how they get rid of them. Hershko's group studied the question in immature red blood cells. Ciechanover found that the protein-destroying activity needed two separate fractions of the cell extract, and in 1977 and 1978 he identified the key component of one of them as a small, heat-stable protein the team called APF-1.
Working during summer visits with Irwin Rose at the Fox Chase Cancer Center in Philadelphia, Ciechanover, Hershko and Rose discovered in 1979 that APF-1 is attached, in several copies, to proteins that are about to be destroyed. They published the finding in 1980, and colleagues showed that APF-1 was a known protein, ubiquitin. The team went on to identify the three enzymes, E1, E2 and E3, that attach the tag, while other researchers identified the proteasome, the machine that breaks tagged proteins down. The Nobel committee described the tag as a molecular 'kiss of death'.
This tagging system controls cell division, DNA repair, the removal of faulty proteins and parts of the immune response, and when it fails, diseases such as some cancers can result. In 2004 Ciechanover, Hershko and Rose shared the Nobel Prize in Chemistry for the discovery of ubiquitin-mediated protein degradation, making Ciechanover and Hershko among Israel's first Nobel laureates in science.
The discovery has helped produce new medicines. Bortezomib, sold as Velcade, blocks the proteasome at the end of the ubiquitin pathway and kills cancer cells that depend on it. Approved in the United States in 2003, it is widely used to treat multiple myeloma and mantle cell lymphoma and is on the World Health Organization's List of Essential Medicines.
Why it matters
Drugs that target the ubiquitin-proteasome pathway, such as bortezomib, help people with multiple myeloma and other blood cancers live longer.
About Aaron Ciechanover
Haifa-born doctor turned biochemist who helped discover how cells tag unwanted proteins for destruction, knowledge behind cancer drugs such as bortezomib for multiple myeloma. Nobel Prize 2004.
Sources
- Press release: The Nobel Prize in Chemistry 2004 NobelPrize.org
- Aaron Ciechanover, Biographical NobelPrize.org
- Bortezomib Wikipedia
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