A PROTEIN COMPLEX OF TRANSLATIONAL REGULATORS OF GCN4 MESSENGER-RNA IS THE GUANINE NUCLEOTIDE-EXCHANGE FACTOR FOR TRANSLATION INITIATION FACTOR-II IN YEAST
A PROTEIN COMPLEX OF TRANSLATIONAL REGULATORS OF GCN4 MESSENGER-RNA IS THE GUANINE NUCLEOTIDE-EXCHANGE FACTOR FOR TRANSLATION INITIATION FACTOR-II IN YEAST
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DOI：
10.1073/pnas.90.11.5350
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发表时间：
1993-06-01
影响因子：
11.1
通讯作者：
HINNEBUSCH, AG
中科院分区：
文献类型：
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作者：
CIGAN, AM;BUSHMAN, JL;HINNEBUSCH, AG
在酿酒酵母中，蛋白激酶GCN 2对翻译起始因子2（eIF-2）α亚基的磷酸化刺激GCN 4 mRNA的翻译。在哺乳动物细胞中，eIF-2 α的磷酸化抑制eIF-2B（eIF-2的GDP-GTP交换因子）的活性。我们目前的生化证据表明，GCD 1，GCD 2，GCD 6，GCD 7和GCN 3编码的GCN 4的5个翻译调节因子是与eIF-2稳定相互作用的蛋白质复合物的组成部分，并代表了eIF-2B的酵母等效物。在体外，该复合物催化eIF-2上的鸟嘌呤核苷酸交换，并克服了GDP对eIF-2、GTP、Met-起始物tRNA（Met）三元复合物形成的抑制作用。这一发现表明，GCD编码的复合物亚基的突变抑制GCN 4翻译，因为它们模拟eIF-2 α磷酸化降低eIF-2B活性。 我们的研究结果表明，GCN 4的翻译控制涉及减少eIF-2B功能，在哺乳动物细胞中使用的机制，以调节总蛋白质的合成，以应对压力。
In Saccharomyces cerevisiae, phosphorylation of the alpha subunit of translation initiation factor 2 (eIF-2) by protein kinase GCN2 stimulates translation of GCN4 mRNA. In mammalian cells, phosphorylation of eIF-2alpha inhibits the activity of eIF-2B, the GDP-GTP exchange factor for eIF-2. We present biochemical evidence that five translational regulators of GCN4 encoded by GCD1, GCD2, GCD6, GCD7, and GCN3 are components of a protein complex that stably interacts with eIF-2 and represents the yeast equivalent of eIF-2B. In vitro, this complex catalyzes guanine nucleotide exchange on eIF-2 and overcomes the inhibitory effect of GDP on formation of eIEF-2.GTP.Met-initiator tRNA(Met) ternary complexes. This finding suggests that mutations in GCD-encoded subunits of the complex derepress GCN4 translation because they mimic eIF-2alpha phosphorylation in decreasing eIF-2B activity. Our results indicate that translational control of GCN4 involves a reduction in eIF-2B function, a mechanism used in mammalian cells to regulate total protein synthesis in response to stress.