Abstract
When transiently expressed in the COS-1 cell, a mutant chimeric protein with an uncleavable glycosylphosphatidylinositol (GPI) -anchor signal failed to be modified by GPI and undergoes rapid degradation in a pre-Golgi compartment. Among several protease inhibitors, 3,4-dichloroisocoumarin and N-acetyl-L-leucinyl-L-leucinyl-L-norleucinal, potent inhibitors of the proteasome, strongly inhibited the degradation of the mutant protein. Furthermore, lactacystin, a highly specific inhibitor of the proteasome, was found to block the degradation. These results suggest that the pre-Golgi degradation pathway is functionally linked to the proteolytic system dependent on the proteasome, which hitherto was believed to play a role mostly in the cytoplasm and nucleus.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcysteine / analogs & derivatives*
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Acetylcysteine / pharmacology
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Animals
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Carrier Proteins / biosynthesis
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Carrier Proteins / metabolism*
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Cell Line
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Chlorocebus aethiops
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Cysteine Endopeptidases / metabolism*
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Cysteine Proteinase Inhibitors / pharmacology*
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Endoplasmic Reticulum Chaperone BiP
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Glycosylphosphatidylinositols / metabolism*
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Golgi Apparatus / metabolism
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Heat-Shock Proteins / metabolism
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Kinetics
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Molecular Chaperones / biosynthesis
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Molecular Chaperones / metabolism*
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Multienzyme Complexes / metabolism*
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Protease Inhibitors / pharmacology*
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Proteasome Endopeptidase Complex
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Rats
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / metabolism
Substances
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Carrier Proteins
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Cysteine Proteinase Inhibitors
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Endoplasmic Reticulum Chaperone BiP
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Glycosylphosphatidylinositols
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Heat-Shock Proteins
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Molecular Chaperones
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Multienzyme Complexes
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Protease Inhibitors
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Recombinant Fusion Proteins
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lactacystin
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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Acetylcysteine