PEST sequences are signals for rapid intracellular proteolysis.

Many features of a protein can enhance its degradation within cells. Unlike thermal lability or oxidizability which increase the likelihood of damage, PEST sequences are built-in signals for destruction. These stretches of polypeptide chain rich in proline (P), glutamate (E), serine (S) and threonine (T) are invariably found in rapidly degraded enzymes, transcriptional factors and components of receptor signalling pathways. They are, by contrast, rarely present among long-lived cellular proteins. In this brief essay, I review the properties of PEST sequences, recent experimental support for the idea that they are indeed proteolytic signals, and possible pathways for catabolism of PEST proteins.