Targets of programmed destruction: a primer to regulatory proteolysis in yeast

Proteasome-mediated proteolysis of defined target proteins is an important regulatory mechanism, which contributes to control of various essential pathways and programs of the eukaryotic cell. Here, I describe basic principles and mechanisms of regulatory proteolysis as observed in a prominent model cell, the yeast Saccharomyces cerevisiae. Selective proteolysis is important for balancing of a cell's proteins. It is used to directly limit or neutralize enzymes in response to defined signals. Proteasome-mediated degradation is also crucial for the regulation of gene transcription. Elimination of transcription factors as well as mobilization of transcriptional activators by limited proteolysis is involved in negative and positive control of transcription. Moreover, recent data indicate that the proteasomal degradation system may be spatially linked to the transcription machinery. Selective proteolytic destruction of regulators and structural proteins is an essential regulatory mechanism ideally designed for the regulation and correct execution of unidirectional processes as are the cell division cycle or the program of apoptotic cell death. Here the proteasomal degradation system acts on various levels.