Glucose-mediated phosphorylation converts the transcription factor Rgt1 from a repressor to an activator
Glucose-mediated phosphorylation converts the transcription factor Rgt1 from a repressor to an activator
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DOI：
10.1074/jbc.m212802200
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发表时间：
2003-03-21
影响因子：
4.8
通讯作者：
Özcan, S
中科院分区：
文献类型：
--
作者：
Mosley, AL;Lakshmanan, J;Özcan, S
葡萄糖是最丰富的碳和能量来源，调节自身有效代谢所需的基因表达。在酵母菌中，葡萄糖通过调节转录因子Rgt1的活性诱导己糖转运蛋白（HXT）基因的表达，Rgt1在葡萄糖缺失时起抑制作用。然而，在高浓度葡萄糖的存在下，Rgt1从抑制因子转化为激活因子，并且是最大程度诱导HXT1基因表达所必需的。我们报道Rgt1仅在没有葡萄糖的情况下与LXT1启动子结合，这表明Rgt1通过间接机制在高葡萄糖水平下增加HXT1基因的表达。Rgt1很可能在高浓度葡萄糖下刺激HXT1基因激活因子的表达。此外，我们证明了Rgt1在高葡萄糖水平下会过度磷酸化，并且这种磷酸化。事件是Rgt1激活转录所必需的。此外，Rgt1在snf3 rgt2和grr1突变体中缺乏葡萄糖介导的磷酸化，这两个突变体在葡萄糖诱导HXT基因表达方面存在缺陷。在这些突变体中，Rgt1表现为独立于碳源的组成抑制因子。我们得出结论，磷酸化。Rgt1对葡萄糖的反应需要消除Rgt1介导的HXT基因抑制，并将Rgt1从转录抑制因子转化为激活因子。
Glucose, the most abundant carbon and energy source, regulates the expression of genes required for its own efficient metabolism. In the yeast Saccharomyces cerevisiae, glucose induces the expression of the hexose transporter (HXT) genes by modulating the activity of the transcription factor Rgt1 that functions as a repressor when glucose is absent. However, in the presence of high concentrations of glucose, Rgt1 is converted from a repressor to an activator and is required for maximal induction of HXT1 gene expression. We report that Rgt1 binds to the LXT1 promoter only in the absence of glucose, suggesting that Rgt1 increases HXT1 gene expression at high levels of glucose by an indirect mechanism. It is likely that Rgt1 stimulates the expression of an activator of the HXT1 gene at high concentrations of glucose. In addition, we demonstrate that Rgt1 becomes hyperphosphorylated in response to high glucose levels and that this phosphorylation. event is required for Rgt1 to activate transcription. Furthermore, Rgt1 lacks the glucose-mediated phosphorylation in the snf3 rgt2 and grr1 mutants, which are defective in glucose induction of HXT gene expression. In these mutants, Rgt1 behaves as a constitutive repressor independent of the carbon source. We conclude that phosphorylation. of Rgt1 in response to glucose is required to abolish the Rgt1-mediated repression of the HXT genes and to convert Rgt1 from a transcriptional repressor to an activator.