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Microtubule-active Drugs Taxol, Vinblastine, and Nocodazole Increase the Levels of Transcriptionally Active p53¹

Joint Center for Radiation Therapy, Boston, Massachusetts 02115

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 p21^WAF1/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.

¹ Supported by funds from the Joint Center for Radiation Therapy.

² To whom requests for reprints should be addressed, at Joint Center for Radiation Therapy, 50 Binney Street, Boston, MA 02115.

Received 7/24/95. Accepted 11/ 1/95.

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