Methods that allow for the manipulation of genes or their products have been 
highly fruitful for biomedical research. Here, we describe a method that allows 
the control of protein abundance by a genetically encoded regulatory system. We 
developed a dormant N-degron that can be attached to the N-terminus of a protein 
of interest. Upon expression of a site-specific protease, the dormant N-degron 
becomes deprotected. The N-degron then targets itself and the attached protein 
for rapid proteasomal degradation through the N-end rule pathway. We use an 
optimized tobacco etch virus (TEV) protease variant combined with selective 
target binding to achieve complete and rapid deprotection of the N-degron-tagged 
proteins. This method, termed TEV protease induced protein inactivation (TIPI) 
of TIPI-degron (TDeg) modified target proteins is fast, reversible, and 
applicable to a broad range of proteins. TIPI of yeast proteins essential for 
vegetative growth causes phenotypes that are close to deletion mutants. The 
features of the TIPI system make it a versatile tool to study protein function 
in eukaryotes and to create new modules for synthetic or systems biology.