Drugs affecting microtubule dynamics increase alpha-tubulin mRNA accumulation via transcription in Tetrahymena thermophila.
In cultured mammalian cells, an increase in the amount of tubulin monomer due to treatment with a microtubule-depolymerizing agent results in a rapid decline in tubulin synthesis. This autoregulatory response is mediated through a posttranscriptional mechanism which decreases the stability of tubulin message with no change in transcriptional activity of tubulin genes. Conversely, treatment with a microtubule-polymerizing drug, such as taxol, results in a slight increase in the synthesis of tubulin. Surprisingly, we find that two microtubule-depolymerizing agents, colchicine and oryzalin, actually cause an increase in alpha-tubulin synthesis and alpha-tubulin message in starved Tetrahymena thermophila. This increase is paralleled by an increase in transcription of alpha-tubulin sequences measured by run-on transcription, while the half-life of tubulin message measured by decay in the presence of actinomycin D does not change appreciably. Treatment of starved cells with taxol also produces an increase in alpha-tubulin synthesis via an increase in message abundance due to an increase in transcription of the alpha-tubulin gene. These results indicate that tubulin synthesis in T. thermophila is regulated very differently than in cultured mammalian cells.
Stargell
L A
LA
Department of Biology, University of Rochester, New York 14627.
Heruth
D P
DP
Gaertig
J
J
Gorovsky
M A
MA
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D003078:Colchicine / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004136:Dinitrobenzenes / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005508:Food Deprivation; D007150:Immunohistochemistry; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism*; D017239:Paclitaxel; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D013424:Sulfanilamides; D016808:Tetrahymena thermophila / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D000470:Alkaloids; D004136:Dinitrobenzenes; D012333:RNA, Messenger; D013424:Sulfanilamides; D014404:Tubulin; D003571:Cytochalasin B; C012465:oryzalin; D014700:Verapamil; D017239:Paclitaxel; D003078:Colchicine