EVIDENCE THAT GCD6 AND GCD7, TRANSLATIONAL REGULATORS OF GCN4, ARE SUBUNITS OF THE GUANINE-NUCLEOTIDE EXCHANGE FACTOR FOR EIF-2 IN SACCHAROMYCES-CEREVISIAE
EVIDENCE THAT GCD6 AND GCD7, TRANSLATIONAL REGULATORS OF GCN4, ARE SUBUNITS OF THE GUANINE-NUCLEOTIDE EXCHANGE FACTOR FOR EIF-2 IN SACCHAROMYCES-CEREVISIAE
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DOI：
10.1128/mcb.13.3.1920
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发表时间：
1993-03-01
影响因子：
5.3
通讯作者：
HINNEBUSCH, AG
中科院分区：
文献类型：
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作者：
BUSHMAN, JL;ASURU, AI;HINNEBUSCH, AG
饥饿酵母酿酒酵母的氨基酸信号增加GCN 4的翻译，GCN 4是氨基酸生物合成基因的转录激活因子。我们已经分离和鉴定了GCD 6和GCD 7基因，并表明它们的产物在非饥饿条件下抑制GCN 4翻译是必需的。我们发现，GCD 6和GCD 7显示序列相似性的高分子量复合物（GCD复合物），似乎是翻译起始因子2B（eIF-2B），催化GDP-GTP交换eIF-2的酵母等效组件。此外，我们表明，GCD 6是30%相同的eIF-2B从兔网织红细胞分离的最大亚基。GCD 6或GCD 7的缺失是致命的，这些基因中的非致命突变以与eIF-2或GCD复合物的已知亚基缺陷相同的方式增加GCN 4的翻译; GCN 4的去抑制依赖于GCN 4 mRNA前导序列中的短开放阅读框，并且独立于蛋白激酶GCN 2引起的eIF-2 α磷酸化而发生，这通常是刺激GCN 4翻译所必需的。总之，我们的结果提供了证据，GCD 6和GCD 7是S.并进一步暗示这种GDP-GTP交换因子在基因特异性翻译控制。
Starvation of the yeast Saccharomyces cerevisiae for an amino acid signals increased translation of GCN4, a transcriptional activator of amino acid biosynthetic genes. We have isolated and characterized the GCD6 and GCD7 genes and shown that their products are required to repress GCN4 translation under nonstarvation conditions. We find that both GCD6 and GCD7 show sequence similarities to components of a high-molecular-weight complex (the GCD complex) that appears to be the yeast equivalent of translation initiation factor 2B (eIF-2B), which catalyzes GDP-GTP exchange on eIF-2. Furthermore, we show that GCD6 is 30% identical to the largest subunit of eIF-2B isolated from rabbit reticulocytes. Deletion of either GCD6 or GCD7 is lethal, and nonlethal mutations in these genes increase GCN4 translation in the same fashion described for defects in known subunits of eIF-2 or the GCD complex; derepression of GCN4 is dependent on short open reading frames in the GCN4 mRNA leader and occurs independently of eIF-2alpha phosphorylation by protein kinase GCN2, which is normally required to stimulate GCN4 translation. Together, our results provide evidence that GCD6 and GCD7 are subunits of eIF-2B in S. cerevisiae and further implicate this GDP-GTP exchange factor in gene-specific translational control.