Proteins that are relatively metabolically stable, with half-lives often exceeding the generation time coexist in the same cell with short-lived proteins that are rapidly degraded. The turnover rates of proteins depend on the physiological state of the cell, and the stability of individual proteins is subject to differential regulation. Metabolic instability is characteristic of damaged or otherwise abnormal proteins, and of many regulatory proteins. A short half-life allows for rapid adjustment of a proteins intracellular concentration through changes in its rate of synthesis or degradation. One important aspect of regulating a protein’s activity through degradation is that it is irreversible. Only de novo synthesis, which can be regulated at the level of either transcription or translation, will result in a reappearance or increase of the respective activity. Another advantage of using degradation as a regulatory device is that it ascertains complete removal of a protein, thereby terminating its interactions with various partners via multiple domains, a task difficult to accomplish by reversible protein modifications such as phosphorylation.