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 lev els of the nuclear phosphoprotein p53 and to induce p53-dependent proc esses. We examined the ability of three microtubule-active agents, tax ol, vinblastine, and nocodazole, to increase p53 levels and activate p 53-dependent processes. When tested using a p53 DNA-binding assay, all three agents induced p53 in a dose-dependent manner. To varying degre es, these agents also induced p21(WAF1/CIP1) mRNA and transcription in a chloramphenicol acetyl transferase reporter system. These data sugg est there is an additional pathway for activating p53 and subsequent p 53-dependent processes.