Regulation of Protein Degradation.

Abstract

of understanding of how to preserve in vivo proteolytic activities in vitro also has interfered with the identification, purification, and analyses of proteinases. Although studies using heterologous proteins or synthetic peptide substrates will continue to provide valuable information, such studies must at some point utilize in vivo substrates if the physiological roles of proteinases are to be defined. Finally, no particular global feature of proteins can be correlated with in vivo stability, again indicating the diversity of mechanisms present. Proteins may be subjected to a limited number of proteolytic cleavages either in the process of intracellular targeting to their final destination or in the maturation of the initial translation product to produce a biologically active mature molecule. This review does not discuss these events but rather focuses on what is known about the events that regulate, orare responsible for, the initial cleavages of a protein ultimately destined for hydrolysis to free amino acids. Our current understanding of the protein degradation process is that it occurs in stages, with the initial endoproteolytic cleavage(s) being more species specific and rate limiting than subsequent hydrolysis to free amino acids by less specific endo- and exopeptidases. For this reason, this review limits discussion to endoproteinases, which are referred to here simply as proteinases. Recent advances in our understanding of the regulation of protein degradation have been made on two fronts: first, in the identification of proteinases, changes in whose activity and/or abundance could or do result in the degradation of previously stable protein(s); and second, in the identification of structural changes in proteins that increase their susceptibility to proteolysis. Advances in these two areas made after a previous review on plant proteolysis (Vierstra, 1993) are elaborated in the following discussions. Recently, multiple cases have been documented in which increases in the levels of mRNAs encoding proteinases occur in response to developmental or environmental changes. The physiological significance of such increases remains unknown; however, they indicate physiological responses that may be mediated by proteolysis or that result in accelerated proteolysis and are therefore mentioned here. Cell cycle progression in eukaryotes represents an exquisite example of the importance of regulated protein degradation, and recent data regarding proteolysis and cell cycle transitions are discussed. A brief description of the diversity of proteinases present in plants is presented, focusing on recent work on