Expression control of the AMPK regulatory subunit and its functional significance in yeast ER stress response.
Expression control of the AMPK regulatory subunit and its functional significance in yeast ER stress response.
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DOI：
10.1038/srep46713
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发表时间：
2017-04-21
影响因子：
4.6
通讯作者：
Mizuno T
中科院分区：
文献类型：
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作者：
Kimura Y;Irie K;Mizuno T
AMPK是一种进化上保守的异三聚体蛋白激酶复合体，由一个催化亚基α和两个调节亚基β和γ组成。此前，我们证明了酿酒酵母AMPK的同源基因Snf1在内质网应激反应中负向调节未折叠蛋白应答(UPR)通路和Hog1 MAP激酶通路。然而，目前尚不清楚SNF1复合体的另外三个β亚基SIP1、SIP2和Gal83如何参与内质网应激反应。在这里，我们表明Gal83在Snf1介导的UPR和Hog1通路的下调中发挥了重要作用。Gal83是正常状态下含量最丰富的β亚基，受内质网应激进一步诱导。这种诱导是通过UPR激活GAL83启动子来实现的。当在GAL83启动子控制下表达时，Sip2显示出相当于Gal83的强大功能活性。我们的结果表明，SnF1AMPK的β亚单位在内质网应激反应中的功能意义是通过调节启动子的活性来调节表达水平。
AMP-activated protein kinase (AMPK) is an evolutionarily conserved heterotrimeric kinase complex consisting of a catalytic subunit, α, and two regulatory subunits, β and γ. Previously, we demonstrated that Snf1, the Saccharomyces cerevisiae ortholog of AMPK, negatively regulates the unfolded protein response (UPR) pathway and the Hog1 MAP kinase pathway in ER stress response. However, it remains unclear how the alternate three β subunits, Sip1, Sip2, and Gal83, of the Snf1 complex participate in ER stress response. Here, we show that Gal83 plays a major role in Snf1-mediated downregulation of the UPR and Hog1 pathways. Gal83 is the most abundant β subunit in the normal state and further induced by ER stress. This induction is mediated via activation of the GAL83 promoter by the UPR. When expressed under the control of the GAL83 promoter, Sip2 exhibits potent functional activity equivalent to Gal83. Our results suggest that the functional significance of the β subunit of Snf1 AMPK in ER stress response is defined by modulation of the expression level through regulation of the promoter activity.