Ubiquitin researchers win Nobel

Ciechanover, Hershko, and Rose awarded for discovery of ubiquitin-mediated proteolysis

Oct 6, 2004
Stephen Pincock(Stephen@thescientisteurope.com)

Three researchers who made fundamental breakthroughs in understanding ubiquitin-mediated proteolysis have been awarded the 2004 Nobel Prize in Chemistry, the Royal Swedish Academy of Sciences said on Wednesday (October 6).

Aaron Ciechanover and Avram Hershko, from the Israel Institute of Technology, Haifa, and Irwin Rose, of the University of California, Irvine, will share the prize for their discoveries in the 1970s and 1980s that began to reveal the central role of the tiny 76-amino acid protein in numerous cellular processes.

"Thanks to the work of the three laureates, it is now possible to understand at a molecular level how the cell controls a number of central processes by breaking down certain proteins and not others," the academy said.

"Without doubt they deserve this prize," John Mayer, professor of molecular cell biology at the University of Nottingham, told The Scientist. "Protein modification by ubiquitylation is just as important as protein phosphorylation for what goes on in the cell."

Ubiquitin-mediated protein degradation governs processes as varied as cell division, DNA repair, quality control of newly produced proteins, and parts of the immune system. Problems with the ubiquitin–proteosome system are implicated in human diseases including cervical cancer and cystic fibrosis.

"The reason they've got this Nobel Prize is because ubiquitin is attached to proteins in different ways not only for degradation, but also to make other things happen in the cell," Mayer added.

A lot of their work was done during sabbatical breaks that Hershko and Ciechanover spent with Rose at the Fox Chase Cancer Center in Philadelphia. Beginning with a paper in 1978, the three laureates published a series of biochemical studies that revealed and characterized the ubiquitin system. Two papers published in PNAS in 1980, which started to explain the role of ubiquitin in adenosine triphosphate–dependent proteolysis, are considered pivotal.

"The possibilities arising from their work in a whole range of fields are enormous," Michael J. Tisdale, professor of cancer biochemistry at Aston University, Birmingham, told The Scientist. "The discovery has opened up a whole new perspective into a number of disease states and allows a more rational means for targeting therapies."

In 2000, Ciechanover and Hershko, along with Alexander Varshavsky, California Institute of Technology, Pasadena, won the Lasker Prize for Basic Medical Research.

In 2002, Hershko and Varshavsky were awarded the American Society for Cell Biology's EB Wilson Medal for their discovery of the ubiquitin system and its functions.