Regulation of the G1 to S transition by the ubiquitin pathway

This, ear the most prestigious prize in sciences, the Lasker Award, has bee n presented to the three scientists who discovered the ubiquitin pathway: A aron Ciechanover, Avram Hershko, and Alexander Varshavsky [Nature Med. 6 (2 000) 1073-1081]. During a time when the scientific community was focused on understanding how proteins were synthesized, they intently pursued the nov el idea that cells were programmed to selectively destroy proteins. Their w ork led to the identification of an elaborate system of protein degradation targeting a myriad of cellular substrates. A small protein called ubiquiti n is at the center of this process. Although the ubiquitin pathway was firs t described in the early 1980s, it has only more recently advanced to the f orefront of basic research as a significant regulatory network within the c ell. The field continues to grow as new ubiquitination enzymes and novel fu nctions of this system are identified. Scientists are focused on elucidatin g the mechanisms by which cells deploy the ubiquitin pathway to control lev els of selected proteins, such as cell cycle regulatory proteins, transcrip tion factors and signaling molecules. Accelerated or decelerated rates of d egradation of particular substrates participate in the genesis of many huma n diseases. Thus, understanding the mechanisms that confer specificity to t he ubiquitin system will allow the development of novel therapeutic approac hes to target aberrations in this pathway underlying tumorigenesis and othe r human pathologies. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.