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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
Author(s) -
FigueiredoPereira Maria E.,
Berg Kelly A.,
Wilk Sherwin
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.63041578.x
Subject(s) - proteasome , calpain , ubiquitin , biochemistry , neurodegeneration , proteasome inhibitor , chemistry , proteolysis , cell culture , microbiology and biotechnology , chymotrypsin , biology , enzyme , trypsin , medicine , genetics , disease , pathology , gene
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.