Grr1-dependent inactivation of Mth1 mediates glucose-induced dissociation of Rgt1 from HXT gene promoters
Grr1-dependent inactivation of Mth1 mediates glucose-induced dissociation of Rgt1 from HXT gene promoters
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DOI：
10.1091/mbc.e03-03-0135
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发表时间：
2003-08-01
影响因子：
3.3
通讯作者：
Wittenberg, C
中科院分区：
文献类型：
--
作者：
Flick, KM;Spielewoy, N;Wittenberg, C
在芽殖酵母中，编码己糖透酶的HXT基因通过F盒蛋白Grr 1拮抗转录抑制子Rgt 1的活性的机制被葡萄糖诱导。Rgt 1失活的机制和Grr 1在该过程中的作用都还不清楚。我们发现，葡萄糖促进Rgt 1的磷酸化和其从HXT基因启动子的解离。这种级联事件取决于F-box蛋白Grr 1。Rgt 1的失活足以解释Grr 1的需要，但不涉及Rgt 1蛋白水解或泛素化。我们发现，Mth 1和Std 1，已知的负调节HXT基因表达的失活，导致Rgt 1的过度磷酸化和它的解离HXT启动子，即使在没有葡萄糖。此外，Mth 1和Std 1的失活绕过了Grr 1诱导这些事件的需要，这表明它们是Grr 1失活的靶点。与该提议一致，Mth 1通过需要Grr 1的机制响应于葡萄糖而迅速消除。基于这些数据，我们提出，葡萄糖通过Grr 1的行为，以促进Mth 1的降解。Mth 1的降解导致Rgt 1从HXT启动子磷酸化和解离，从而激活HXT基因表达。
In budding yeast, HXT genes encoding hexose permeases are induced by glucose via a mechanism in which the F box protein Grr1 antagonizes activity of the transcriptional repressor Rgt1. Neither the mechanism of Rgt1 inactivation nor the role of Grr1 in that process has been understood. We show that glucose promotes phosphorylation of Rgt1 and its dissociation from HXT gene promoters. This cascade of events is dependent upon the F-box protein Grr1. Inactivation of Rgt1 is sufficient to explain the requirement for Grr1 but does not involve Rgt1 proteolysis or ubiquitination. We show that inactivation of Mth1 and Std1, known negative regulators of HXT gene expression, leads to the hyperphosphorylation of Rgt1 and its dissociation from HXT promoters even in the absence of glucose. Furthermore, inactivation of Mth1 and Std1 bypasses the requirement for Grr1 for induction of these events, suggesting they are targets for inactivation by Grr1. Consistent with that proposal, Mth1 is rapidly eliminated in response to glucose via a mechanism that requires Grr1. Based upon these data, we propose that glucose acts via Grr1 to promote the degradation of Mth1. Degradation of Mth1 leads to phosphorylation and dissociation of Rgt1 from HXT promoters, thereby activating HXT gene expression.