October 7, 2004 -- The 2004 Nobel Prize in Chemistry has been awarded to three scientists who found the "kiss of death" for proteins. Aaron Ciechanover and Avram Hershko of the Technion Israel Institute of Technology in Haifa, Israel and Irwin Rose of the University of California, Irvine shared this year's prize "for the discovery of ubiquitin-mediated protein degradation."
The Kiss of Death
The "kiss of death" for proteins is called ubiquitin. It is
itself a protein, a tiny one consisting of only 76 amino
acids. It acts as the "kiss of death" for other proteins.
In the normal course of events, proteins need to be broken down and their parts recycled. This is done, it turns out, by tagging proteins with ubiquitin, a process called ubiquination.
Ubiquitin is the signal to the cell's transport machinery to ferry a protein to the proteasome, a barrel-shaped chamber floating in the cell cytoplasm. Proteasomes then slice the protein into bits that are recycled into new proteins.
Antagonizing this process are enzymes that remove ubiquitin from proteins and prevent them being degraded.
Ubiquitin is Ubiquitous
Ubiquitin is appropriately named
since it is ubiquitous
. It
is present in all types of cells.
Ubiquitin is also one of the most highly conserved (least changed) of all proteins during evolution. The sequence of the amino acids that make up ubiquitin is identical in all creatures from fungi and yeast to insects, frogs, and mice to humans. Evolution has not changed ubiquitin one iota.
Inventory Control System
The ubiquitin system is much more than just "waste
disposal." Rather, the system acts as an inventory control
program. The rapid removal of specific proteins by ubiquitin
tells the cell when to turn on or turn off its other
functions and when to die. Examples of processes governed by
ubiquitin are cell division, DNA repair, the quality control
of newly produced proteins, and important parts of the
immune defense. When the degradation does not work
correctly, we fall ill. Cervical cancer and cystic fibrosis
are two examples noted by the Nobel Committee.
An Essential System
So important is the ubiquitin system that about 1,000 of the
35,000 genes in the human genome appear to take part in the
ubiquitin system. Ubiquitin is so essential that shortly
before the protein is squeezed into the proteasome, its
ubiquitin tag is removed for reuse.
Knowledge of ubiquitin offers the opportunity to develop drugs against diseases. In 2003, the US Food and Drug Administration approved a drug called Velcade, which interferes with the workings of the proteasomes as a treatment for multiple myeloma, a cancer of the bone marrow.
International Medical Research
The media
announced that this year's Nobel Prize in Chemistry went to one American and two
Israelis but in a sense that is misleading. The countries from which they come
matters less than the international nature of their work
The American Irwin Rose and Avram Hershko from Israel met at a meeting in 1979. They realized that they were working on the same problem and began a scientific collaboration. Soon Ciechanover, a graduate student of Hershko's, joined the collaboration.
Much of the research that won this Nobel Prize was done during a series of sabbatical leaves that Hershko and Ciechanover took over two decades with Irwin Rose, then at the Fox Chase Cancer Center in Philadelphia.
Medical research transcends national boundaries.
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