DRUGS AFFECTING MICROTUBULE DYNAMICS INCREASE ALPHA-TUBULIN MESSENGER-RNA ACCUMULATION VIA TRANSCRIPTION IN TETRAHYMENA-THERMOPHILA
DRUGS AFFECTING MICROTUBULE DYNAMICS INCREASE ALPHA-TUBULIN MESSENGER-RNA ACCUMULATION VIA TRANSCRIPTION IN TETRAHYMENA-THERMOPHILA
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DOI：
10.1128/mcb.12.4.1443
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发表时间：
1992-04-01
影响因子：
5.3
通讯作者：
GOROVSKY, MA
中科院分区：
文献类型：
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作者：
STARGELL, LA;HERUTH, DP;GOROVSKY, MA
在培养的哺乳动物细胞中，由于微管解聚剂处理导致微管蛋白单体数量增加，导致微管蛋白合成迅速下降。这种自我调节反应是通过转录后机制介导的，这种机制降低了微管蛋白信息的稳定性，而不改变微管蛋白基因的转录活性。相反，用微管聚合药物治疗，如紫杉醇，会导致微管蛋白的合成略有增加。令人惊讶的是，我们发现两种微管解聚剂秋水仙碱和谷氮灵实际上导致了饥饿的嗜热四膜虫α-微管蛋白合成和α-微管蛋白信息的增加。这种增加与通过连续转录测量的α-微管蛋白序列的转录增加是平行的，而通过在放线菌素D存在下衰变来测量微管蛋白信息的半衰期没有明显的变化。用紫杉醇处理饥饿的细胞还可以通过增加α-微管蛋白基因的转录而增加信息丰度，从而增加α-微管蛋白的合成。这些结果表明，嗜热支原体中微管蛋白的合成与培养的哺乳动物细胞中的微管蛋白合成有很大的不同。
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.