Abstract

Diverse vacuolar and nonvacuolar pathways of protein degradation have been described in yeast. In several cases, much is known about the proteases involved, but most of these studies utilized nonphysiological model substrates. On the other hand, many regulatory proteins, such as those involved in cell cycle control, cell type determination, and the regulation of metabolite fluxes through biosynthetic pathways, have been shown to be rapidly and selectively destroyed in vivo, either constitutively or in response to specific regulatory signals. Precisely what molecular features of this class of proteins target them for degradation is largely unknown; this question is an area of intense current interest. A connection has been made between a particular proteolytic mechanism and a specific naturally short-lived protein in only a handful of examples. It is in this regard that the powerful molecular and genetic techniques available in yeast will probably have their greatest impact in the near future. The promise of this type of approach is already becoming apparent with the molecular genetic analysis of the yeast ubiquitin system. Although this work began less than ten years ago, the genes encoding at least 22 proteins involved in ubiquitin-dependent processes have already been isolated, and questions of their physiological and mechanistic function are being answered at an ever quickening pace.