BACKGROUND: Tools for in vivo manipulation of protein abundance or activity are 
highly beneficial for life science research. Protein stability can be 
efficiently controlled by conditional degrons, which induce target protein 
degradation at restrictive conditions.
RESULTS: We used the yeast Saccharomyces cerevisiae for development of a 
conditional, bidirectional degron to control protein stability, which can be 
fused to the target protein N-terminally, C-terminally or placed internally. 
Activation of the degron is achieved by cleavage with the tobacco etch virus 
(TEV) protease, resulting in quick proteolysis of the target protein. We found 
similar degradation rates of soluble substrates using destabilization by the N- 
or C-degron. C-terminal tagging of essential yeast proteins with the 
bidirectional degron resulted in deletion-like phenotypes at non-permissive 
conditions. Developmental process-specific mutants were created by N- or 
C-terminal tagging of essential proteins with the bidirectional degron in 
combination with sporulation-specific production of the TEV protease.
CONCLUSIONS: We developed a system to influence protein abundance and activity 
genetically, which can be used to create conditional mutants, to regulate the 
fate of single protein domains or to design artificial regulatory circuits. 
Thus, this method enhances the toolbox to manipulate proteins in systems biology 
approaches considerably.