Protease/inhibitor mechanisms involved in ATP-dependent proteolysis.
ATP-dependent proteolytic activities constitute a family of distinct enzymes and enzyme complexes which function in the selective degradation of proteins in the cytosol and possibly other non-lysosomal cellular compartments. In reticulocytes as well as other eukaryotic cells, conjugation of the polypeptide ubiquitin to proteins, an ATP-requiring process, is important for proteolysis. However, the popular view that ubiquitin functions by tagging substrates for recognition by conjugate-specific proteases should be viewed with caution. Evidence is reviewed implicating an ATP-independent high molecular weight protease (HMP) which can degrade non-ubiquitinated proteins in the ATP-dependent pathway. This protease consists of several related subunits based upon monoclonal antibody studies. HMP by itself, can account for effects of substrate amino group blockage on ATP-dependent proteolysis. Endogenous inhibitors (40 kDa and 50 kDa) have been isolated and shown to block HMP non-competitively. Unlike the soluble system in reticulocytes, the major ATP-dependent activity in mouse erythroleukemia cells is particulate in aqueous media but soluble in the presence of sucrose. Despite such differences, evidence suggests analogous inhibitory components in this system. The possibility that protease/inhibitor interaction is regulated by ATP and ubiquitin in different systems is discussed.
Etlinger
J D
JD
Department of Cell Biology and Anatomy, New York Medical College, Valhalla 10595.
Gu
M
M
Li
X
X
Weitman
D
D
Rieder
R F
RF
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors; D007700:Kinetics; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology; D051379:Mice; D008970:Molecular Weight; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D011480:Protease Inhibitors / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism*; D014452:Ubiquitins / Q000502:physiology*
D000911:Antibodies, Monoclonal; D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D011480:Protease Inhibitors; D011506:Proteins; D014452:Ubiquitins; D000255:Adenosine Triphosphate; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex