Ectopic targeting of substrates to the ubiquitin pathway.

Explanation of the physiological function of a cellular protein often requires targeted removal of that protein to reveal the associated biochemical and phenotypic alterations. A variety of technologies such as gene targeting and RNAi have been developed to abrogate the biosynthesis of the protein of interest. Recently, targeted protein degradation by harnessing the cellular ubiquitin-proteolytic machinery has emerged as a novel reverse genetic tool for loss-of-function studies. Targeted proteolysis operates at the posttranslational level to directly accelerate the turnover rate of the target protein and opens up new avenues for the dissection of complicated protein functions associated with posttranslational events, which are unattainable by a simple blocking of the biosynthesis of the target protein.