Receptor for activated C-kinase (RACK1) homolog Cpc2 facilitates the general amino acid control response through Gcn2 kinase in fission yeast
Receptor for activated C-kinase (RACK1) homolog Cpc2 facilitates the general amino acid control response through Gcn2 kinase in fission yeast
复制标题
裂殖酵母中活化 C 激酶 (RACK1) 同源物 Cpc2 的受体通过 Gcn2 激酶促进一般氨基酸控制反应
DOI：
10.1074/jbc.m112.445270
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
F.
中科院分区：
文献类型：
--
作者：
Tarumoto;Y. Kanoh;J. Ishikawa;F.
一般氨基酸控制（GAAC）是至关重要的传感和适应养分的可用性。氨基酸饥饿激活蛋白激酶Gcn 2，其通过磷酸化真核起始因子2（eIF 2 α）的α-亚基在GAAC反应中起核心作用，导致翻译开关以刺激应激反应基因的选择性表达。我们在这里报告，在裂殖酵母裂殖酵母，Cpc 2，一个同源的哺乳动物受体活化的C-激酶（RACK 1），是重要的GAAC反应。删除S.粟酒裂殖酵母cpc 2损害氨基酸饥饿诱导的eIF 2 α磷酸化和氨基酸生物合成基因的表达，从而使细胞对氨基酸限制严重敏感。与通常抑制GAAC反应的Saccharomycescleae Cpc 2直系同源物不同，我们的研究结果表明，S. pombeCpc 2促进GAAC响应。我们还发现S. pombeCpc 2是饥饿诱导的Gcn 2自磷酸化所必需的，这是Gcn 2功能所必需的。这些结果表明S. pombeCpc 2通过调节Gcn 2的激活促进GAAC反应，并为RACK 1对Gcn 2介导的GAAC反应的调节功能提供了新的见解。背景：一般氨基酸控制（GAAC）对氨基酸饥饿下细胞的存活非常重要。裂殖酵母Cpc 2（哺乳动物RACK 1的同源物）的缺失导致eIF 2 α磷酸化缺陷，氨基酸生物合成基因的诱导，结论：Cpc 2通过促进Gcn 2的激活而促进GAAC反应，意义：本研究为RACK 1同源物促进GAAC反应提供了证据。
General amino acid control (GAAC) is crucial for sensing and adaptation to nutrient availability. Amino acid starvation activates protein kinase Gcn2, which plays a central role in the GAAC response by phosphorylating the α-subunit of eukaryotic initiation factor 2 (eIF2α), leading to the translational switch to stimulate selective expression of stress-responsive genes. We report here that in fission yeastSchizosaccharomyces pombe, Cpc2, a homolog of mammalian receptor for activated C-kinase (RACK1), is important for the GAAC response. Deletion ofS. pombe cpc2impairs the amino acid starvation-induced phosphorylation of eIF2α and the expression of amino acid biosynthesis genes, thereby rendering cells severely sensitive to amino acid limitation. Unlike theSaccharomyces cerevisiaeCpc2 ortholog, which normally suppresses the GAAC response, our findings suggest thatS. pombeCpc2 promotes the GAAC response. We also found thatS. pombeCpc2 is required for starvation-induced Gcn2 autophosphorylation, which is essential for Gcn2 function. These results indicate thatS. pombeCpc2 facilitates the GAAC response through the regulation of Gcn2 activation and provide a novel insight for the regulatory function of RACK1 on Gcn2-mediated GAAC response.Background: General amino acid control (GAAC) is important for cell survival under amino acid starvation.Results: Absence of fission yeast Cpc2, a homolog of mammalian RACK1, causes defects in eIF2α phosphorylation, induction of amino acid biosynthesis genes, and Gcn2 autophosphorylation.Conclusion: Cpc2 stimulates the GAAC response by facilitating Gcn2 activation.Significance: This study provides evidence that RACK1 homolog promotes the GAAC response.