A new inhibitor of the chymotrypsin-like activity of the multicatalytic proteinase complex (20S proteasome) induces accumulation of ubiquitin-protein conjugates in a neuronal cell.
Exposure of HT4 cells (a mouse neuronal cell line) to a new potent permeable peptidyl aldehyde inhibitor of the chymotrypsin-like activity of the multicatalytic proteinase complex (MPC) causes accumulation of ubiquitinylated proteins. In contrast, inhibition of calpain or treatment with a lysosomotropic agent failed to produce detectable ubiquitin-protein conjugates. The appearance of such conjugates is not a nonspecific phenomenon because incubation with the peptidyl alcohol analogue of the inhibitor does not produce accumulation of ubiquitinylated proteins. The MPC inhibitor may therefore be a useful tool for identification and study of physiological pathways involving MPC. Furthermore, the inhibitor may help develop a model for the study of neurodegeneration where accumulation of ubiquitin-protein conjugates is commonly detected in abnormal brain inclusions.
Figueiredo-Pereira
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ME
Department of Pharmacology, Mount Sinai School of Medicine, CUNY, New York 10029.
Berg
K A
KA
Wilk
S
S
D000818:Animals; D015153:Blotting, Western; D002417:Cattle; D002460:Cell Line; D002918:Chymotrypsin / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000302:isolation & purification / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D007700:Kinetics; D051379:Mice; D009097:Multienzyme Complexes / Q000302:isolation & purification / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000302:isolation & purification / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010902:Pituitary Gland / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex; D011499:Protein Processing, Post-Translational; D014452:Ubiquitins / Q000302:isolation & purification / Q000378:metabolism*
D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; D014452:Ubiquitins; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex