Pheromone-induced degradation of Ste12 contributes to signal attenuation and the specificity of developmental fate
Pheromone-induced degradation of Ste12 contributes to signal attenuation and the specificity of developmental fate
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DOI：
10.1128/ec.00270-06
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发表时间：
2006-12-01
期刊：
影响因子：
--
通讯作者：
Errede, Beverly
中科院分区：
文献类型：
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作者：
Esch, R. Keith;Wang, Yuqi;Errede, Beverly
酿酒酵母的 Ste12 转录因子调节控制两种不同发育命运的转录程序。一种是分化为有交配能力的形式，这是对交配信息素的反应。另一个是向丝状生长形式的转变，这是由于营养缺乏而发生的。 Ste12 的这两个不同作用使其成为赋予生物特异性的调控机制研究的焦点。交配分化的瞬时信号特征使我们检验了这样的假设：Ste12 周转的调节可能有助于减弱交配特异性转录程序并限制丝化程序的激活。我们发现，延长信息素诱导会导致泛素介导的不稳定和 Ste12 量减少。信息素刺激培养物中的这种消耗取决于交配途径专用的丝裂原激活蛋白激酶 Fus3 及其目标 Cdc28 抑制剂 Fart。信息素诱导的交配特异性基因转录 (FUS1) 的减弱在时间上与 Ste12 的消耗相关。这种衰减在缺失背景（fus3 Delta 或 far1 Delta）中被消除，其中 Ste12 仍然存在。此外，当 Ste12 水平保持较高水平时，信息素会诱导单倍体入侵和丝状生长，而不是交配分化。这些观察结果表明，Ste12 的缺失会增强对信息素的适应性反应，并有助于减少丝状反应。
The Ste12 transcription factor of Saccharomyces cerevisiae regulates transcription programs controlling two different developmental fates. One is differentiation into a mating-competent form that occurs in response to mating pheromone. The other is the transition to a filamentous-growth form that occurs in response to nutrient deprivation. These two distinct roles for Ste12 make it a focus for studies into regulatory mechanisms that impart biological specificity. The transient signal characteristic of mating differentiation led us to test the hypothesis that regulation of Ste12 turnover might contribute to attenuation of the mating-specific transcription program and restrict activation of the filamentation program. We show that prolonged pheromone induction leads to ubiquitin-mediated destabilization and decreased amounts of Ste12. This depletion in pheromone-stimulated cultures is dependent on the mating-pathway-dedicated mitogen-activated protein kinase Fus3 and its target Cdc28 inhibitor, Fart. Attenuation of pheromone-induced mating-specific gene transcription (FUS1) temporally correlates with Ste12 depletion. This attenuation is abrogated in the deletion backgrounds (fus3 Delta or far1 Delta) where Ste12 is found to persist. Additionally, pheromone induces haploid invasion and filamentous-like growth instead of mating differentiation when Ste12 levels remain high. These observations indicate that loss of Ste12 reinforces the adaptive response to pheromone and contributes to the curtailing of a filamentation response.