N-end rule of selective protein turnover: mechanistic aspects and functional implications

Abstract

In both bacterial and eukaryotic cells, relatively long-lived proteins, whose half-lives are close to or exceed the cell generation time, coexist with proteins whose half-lives can be less than 1% of the cell generation time. Rates of intra-cellular protein degeneration are a function of the cell’s physiological state, and appear to be controlled differentially for individual proteins. In particular, damaged and some otherwise abnormal proteins are metabolically unstable in vivo. Although the specific functions of selective protein degradation are in most cases still unknown, it is clear that many regulatory proteins are extremely short-lived in vivo. Metabolic instability of such proteins allows for rapid adjustments of their intracellular concentrations through regulated changes in rates of their synthesis or degradation.