Ubiquitin and the inflammasome

An aspect of modern molecular biology which I find attractive is the way it generates new vocabulary. Of the two examples of this included in the title of this post, the first is already quite old while the second seems to be a buzzword in certain sectors of the research community at the moment. They were brought together in a talk by Vishva Dixit which I heard yesterday. Dixit is Vice President for Research at Genentech which is one of the biggest biotech companies in the world. He has had an interesting career spanning academia and industry. This is described in an article in Nature, 428, 586.

What is ubiquitin? A classical subject in molecular biology is that of the mechanisms by which proteins are synthesized in cells. The path from the information encoded in DNA to its transcription into RNA and its translation into the sequence of amino acids which make up the protein has been studied intensively. The fact that there is a steady turnover of amino acids in the cell means that it is necessary to complement the synthesis of proteins by a process of degradation in order to maintain a steady state. The process of destruction of proteins must be carefully controlled so as to avoid damaging the cell. It was found that the controlled degradation of protein actually consumes energy. At the centre of this process is the small protein ubiquitin. Several molecules of this substance covalently attached to a target protein mark it for degradation. Ciechanover, Hershko and Rose were awarded the Nobel prize for chemistry in 2004 for the contributions of their experiments to the understanding of this process. More recently it has been found that ubiquitin plays an important role in several other processes such as the regulation of the cell cycle, inflammation and immunity.

The inflammasome is a complex of proteins which plays a role in inflammation. It has relations to the mechanisms involved in apoptosis (programmed cell death) and and it makes use of ubiquitin. Understanding how this complex of proteins works and, perhaps more importantly, what cues activate it, may be important for obtaining better insights into autoimmune diseases such as rheumatoid arthritis and lupus.

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