Abstract
The proteasome is a protease complex responsible for rapid, selective, and irreversible removal of regulatory proteins, as well as many other cellular proteins. In this study, we have demonstrated that a proliferation-associated nuclear protein Ki-67 depended on the proteasome for its rapid degradation. A proteasome-specific inhibitor lactacystin augmented Ki-67 protein levels in pancreatic cancer BxPC-3 cells while repressed the level of steady-state Ki-67 mRNA. Inhibition of the proteasome also led to accumulation of two CDK inhibitors p27(kip1) and p21(cip1) in the BxPC-3 cells. Failed reduction of Ki-67 protein and enhanced levels of the two CDK inhibitors are likely contributing factors for the suppressed BxPC-3 proliferation after proteasome inhibition.
Copyright 2000 Wiley-Liss, Inc.
Publication types
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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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Cell Cycle Proteins*
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Cell Division / drug effects
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases / antagonists & inhibitors
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Cyclins / metabolism
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Cysteine Endopeptidases / metabolism*
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Enzyme Inhibitors / pharmacology
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Fluorescent Antibody Technique
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Gene Expression Regulation
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Humans
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Ki-67 Antigen / metabolism*
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Microscopy, Fluorescence
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Microtubule-Associated Proteins / metabolism
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Multienzyme Complexes / metabolism*
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Proteasome Endopeptidase Complex
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RNA, Messenger / drug effects
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Tumor Cells, Cultured
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Tumor Suppressor Proteins*
Substances
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CDKN1A protein, human
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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Enzyme Inhibitors
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Ki-67 Antigen
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Microtubule-Associated Proteins
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Multienzyme Complexes
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RNA, Messenger
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Tumor Suppressor Proteins
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lactacystin
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Cyclin-Dependent Kinase Inhibitor p27
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Cyclin-Dependent Kinases
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Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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Acetylcysteine