Abstract
A range of DNA-damaging agents has been shown to increase cellular levels of the nuclear phosphoprotein p53 and to induce p53-dependent processes. We examined the ability of three microtubule-active agents, taxol, vinblastine, and nocodazole, to increase p53 levels and activate p53-dependent processes. When tested using a p53 DNA-binding assay, all three agents induced p53 in a dose-dependent manner. To varying degrees, these agents also induced p21WAF1/CIP1 mRNA and transcription in a chloramphenicol acetyl transferase reporter system. These data suggest there is an additional pathway for activating p53 and subsequent p53-dependent processes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Base Sequence
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Cell Cycle / drug effects
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / genetics*
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DNA-Binding Proteins / metabolism
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Gene Expression Regulation / drug effects
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Mice
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Microtubules / drug effects*
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Molecular Sequence Data
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Nocodazole / pharmacology*
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Oligodeoxyribonucleotides / chemistry
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Paclitaxel / pharmacology*
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Promoter Regions, Genetic
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RNA, Messenger / genetics
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Transcription, Genetic / drug effects*
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Tumor Suppressor Protein p53 / genetics*
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Vinblastine / pharmacology*
Substances
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Cdkn1a protein, mouse
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DNA-Binding Proteins
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Oligodeoxyribonucleotides
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RNA, Messenger
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Tumor Suppressor Protein p53
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Vinblastine
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Paclitaxel
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Nocodazole