Mobilizing the proteolytic machine: cell biological roles of proteasome activators and inhibitors.
Proteasomes perform the majority of proteolysis that occurs in the cytosol and nucleus of eukaryotic cells and, thereby, perform crucial roles in cellular regulation and homeostasis. Isolated proteasomes are inactive because substrates cannot access the proteolytic sites. PA28 and PA200 are activators that bind to proteasomes and stimulate the hydrolysis of peptides. Several protein inhibitors of the proteasome have also been identified, and the properties of these activators and inhibitors have been characterized biochemically. By contrast, their physiological roles--which have been reported to include production of antigenic peptides, proteasome assembly and DNA repair--are controversial. In this article, we briefly review the biochemical data and discuss the possible biological roles of PA28, PA200 and proteasome inhibitors.
Rechsteiner
Martin
M
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84132, USA. marty@biochem.utah.edu
Hill
Christopher P
CP
D000818:Animals; D017209:Apoptosis; D001324:Autoantigens / Q000276:immunology / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D007107:Immune System; D009124:Muscle Proteins / Q000276:immunology / Q000502:physiology; D046988:Proteasome Endopeptidase Complex / Q000737:chemistry / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D061988:Proteasome Inhibitors
D001324:Autoantigens; C099558:Ki antigen; D009124:Muscle Proteins; C085047:PSME1 protein, human; D061988:Proteasome Inhibitors; C486207:PSME2 protein, human; D046988:Proteasome Endopeptidase Complex