Protein degradation is a necessity for many reasons: Homeostasis must be maintained while cellular structures are continually rebuilt, in particular during development or in response to external stimuli. Proteins misfolded as a consequence of mutations or ensuing from heat or oxidative stress must be scavenged because they are prone to aggregation. Beyond these more mundane “housekeeping” functions, protein degradation provides a means to terminate the lifespan of many regulatory proteins at distinct times; amongst them are cyclins, transcription factors, and components of signal transduction pathways (for reviews, see