2004年诺贝尔化学奖介绍_化学论文

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The Nobel Prize in Chemistry 2004 – Information for the Public

6 October 2004

A human cell contains some hundred thousand different proteins. These have numerous important functions: as accelerators of chemical reactions in the form of enzymes, as signal substances in the form of hormones, as important actors in the immune defence and by being responsible for the cell's form and structure. This year's Nobel Laureates in chemistry, Aaron Ciechanover, Avram Hershko and Irwin Rose, have contributed ground-breaking chemical knowledge of how the cell can regulate the presence of a certain protein by marking unwanted proteins with a label consisting of the polypeptide ubiquitin. Proteins so labelled are then broken down – degraded – rapidly in cellular "waste disposers" called proteasomes.

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Through their discovery of this protein-regulating system Aaron Ciechanover, Avram Hershko and Irwin Rose have made it possible to understand at molecular level how the cell controls a number of very important biochemical processes such as the cell cycle, DNA repair, gene transcription and quality control of newly-produced proteins. New knowledge of this form of controlled protein death has also contributed to explaining how the immune defence functions. Defects in the system can lead to various diseases including some types of cancer.

Proteins labelled for destruction

Degradation needs no energy – or does it?

While great attention and much research have been spent on understanding how the cell controls the synthesis of a certain protein – at least five Nobel Prizes have been awarded in this area – the reverse, the degradation of proteins, has long been considered less important. A number of simple protein-degrading enzymes were already known. One example is trypsin, which in the small intestine breaks down proteins in our food to amino acids. Likewise, a type of cell organelle, the lysosome, in which proteins absorbed from outside are broken down, had long been studied. Common to these processes is that they do not require energy in order to function.

Experiments as long ago as the 1950s showed, however, that the breakdown of the cell's own proteins does require energy. This long puzzled researchers, and it is precisely this paradox that underlies this year's Nobel Prize in Chemistry: that the breakdown of proteins within the cell requires energy while other protein degradation takes place without added energy. A first step towards an explanation of this energy-dependent protein degradation was taken by Goldberg and his co-workers who in 1977 produced a cell-free extract from immature red blood cells, reticulocytes, which catalyse the breakdown of abnormal proteins in an ATP-dependent manner (ATP = adenosine triphosphate – the cell's energy currency).

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