Fus3-regulated Tec1 degradation throulah SCFCdc4 determines MAPK signaling specificity during mating in yeast
Fus3-regulated Tec1 degradation throulah SCFCdc4 determines MAPK signaling specificity during mating in yeast
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DOI：
10.1016/j.cell.2004.11.053
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发表时间：
2004-12-29
期刊：
影响因子：
64.5
通讯作者：
Liu, HP
中科院分区：
文献类型：
--
作者：
Chou, S;Huang, L;Liu, HP
信号特异性是平行丝裂原活化蛋白激酶（MAPK）级联反应的基础，该级联反应控制响应于不同刺激的生长和分化。在酿酒酵母中，信息素响应MAPK级联的组分激活Fus3和Kss1 MAPK以诱导交配，Kss1以促进交配。主动Fus3需要防止在信息素响应期间激活诱导程序。Fus3如何阻止交叉激活尚不清楚。在这里，我们表明，Tec1，辅因子的Ste12的表达的抑制基因，是迅速降解的信息素反应过程中。Fus3而不是Kss1通过SCFCdc4泛素连接酶诱导Tec1泛素化和降解。预测的高亲和力Cdc4结合基序中的T273在体外和体内均被Fus3磷酸化。Tec1（T273V）阻断Tec1泛素化和降解，并允许响应于信息素诱导表达基因。因此，Fus3通过降解Tec1抑制交配期间的丝状生长。
Signaling specificity is fundamental for parallel mitogen-activated protein kinase (MAPK) cascades that control growth and differentiation in response to different stimuli. In Saccharomyces cerevisiae, components of the pheromone-responsive MAPK cascade activate Fus3 and Kss1 MAPKs to induce mating and Kss1 to promote filamentation. Active Fus3 is required to prevent the activation of the filamentation program during pheromone response. How Fus3 prevents the crossactivation is not clear. Here we show that Tec1, a cofactor of Ste12 for the expression of filamentation genes, is rapidly degraded during pheromone response. Fus3 but not Kss1 induces Tec1 ubiquination and degradation through the SCFCdc4 ubiquitin ligase. T273 in a predicted high-affinity Cdc4 binding motif is phosphorylated by Fus3 both in vitro and in vivo. Tec1(T273V) blocks Tec1 ubiquitination and degradation and allows the induction of filamentation genes in response to pheromone. Thus, Fus3 inhibits filamentous growth during mating by degrading Tec1.