Disordered protein segments affect proteins' half lives and might be an important source of phenotyp

A recently published study in Cell Reports from Madan Babu's lab has brought some sense to the long-known fact that altering a protein's half live has profound effects in diverse processes such as the cell cycle, cell differentiation and development, and circadian rhythms. The precise control of protein turnover is essential for cellular homeostasis, and disordered segments are known to affect a protein's half-life. In an elegant series of analyses, the group of Madan Babu showed that proteins with terminal or internal intrinsically disordered segments have significantly shorter half-lives. Therefore, the acquisition and loss of disordered segments in the course of evolution is likely to have profound effects on cellular signaling processes, and thus constitute an important source of genetic variation in populations with crucial phenotypic consequences. Despite protein turnover being the last step in the gene expression process, its importance has not been understimated by the cell: ubiquitinating enzymes constitute the largest protein superfamily in our genomes (read more).