Microtubule-active drugs taxol, vinblastine, and nocodazole increase the levels of transcriptionally active p53.
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.
Joint Center for Radiation Therapy, Boston, Massachusetts 02115, USA.
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D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008870:Microtubules / Q000187:drug effects*; D008969:Molecular Sequence Data; D015739:Nocodazole / Q000494:pharmacology*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D017239:Paclitaxel / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014747:Vinblastine / Q000494:pharmacology*
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D014747:Vinblastine; D017239:Paclitaxel; D015739:Nocodazole