Shin-biology regulated by protein lifetime

In addition to protein synthesis, protein degradation is an important mechanism that determines protein composition. Research on the mechanisms of intracellular protein degradation has progressed over the past 30 years, and basic mechanisms such as the ubiquitin-proteasome system and autophagy have been identified as large-scale degradation systems. In addition, various proteases exist inside and outside the cell and play essential roles in physiological functions. However, the mechanism by which protein lifetime is determined is still poorly understood. For example, the half-life of proteins in rat neurons varies widely, from less than minutes to more than 10 days. The observation that intracellular proteins have different lifetimes was recognized in 1978 and has been a mystery for half a century. Several laws have been proposed to determine protein lifetimes. The N-terminal rule was first published in 1986, followed by the C-terminal rule and a similar rule called the PEST sequence. However, while these rules can explain the lifetimes of some proteins, they do not explain the lifetimes of most proteins, and the mechanism by which protein lifetimes are determined remains unknown. The mechanism by which protein lifetimes are determined remains unresolved.