PEST SEQUENCES AND REGULATION BY PROTEOLYSIS

In 1986, we proposed that polypeptide sequences enriched in proline (P ), glutamic acid (E), serine (S) and threonine (T) target proteins for rapid destruction. For much of the past decade there were only sporad ic experimental tests of the hypothesis. This situation changed marked ly during the past two years with a number of papers providing strong evidence that PEST regions do, in fact, serve as proteolytic signals. Here, we briefly review the properties of PEST regions and some intere sting examples of the conditional nature of such signals. Most of the article, however, focuses on recent experimental support for the hypot hesis and on mechanisms responsible for the rapid degradation of prote ins that contain PEST regions.