TRANSCRIPTIONAL-TRANSLATIONAL REGULATORY CIRCUIT IN SACCHAROMYCES-CEREVISIAE WHICH INVOLVES THE GCN4 TRANSCRIPTIONAL ACTIVATOR AND THE GCN2 PROTEIN-KINASE
TRANSCRIPTIONAL-TRANSLATIONAL REGULATORY CIRCUIT IN SACCHAROMYCES-CEREVISIAE WHICH INVOLVES THE GCN4 TRANSCRIPTIONAL ACTIVATOR AND THE GCN2 PROTEIN-KINASE
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DOI：
10.1128/mcb.8.5.2132
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发表时间：
1988-05-01
影响因子：
5.3
通讯作者：
HAUGE, BM
中科院分区：
文献类型：
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作者：
ROUSSOU, I;THIREOS, G;HAUGE, BM
Gcn4蛋白通过与酿酒酵母氨基酸生物合成基因5‘-’调控区的DNA序列特异性结合，介导氨基酸生物合成基因的转录激活。Gcn4的表达在翻译水平上受到调控，在氨基酸饥饿的条件下，翻译去阻遏发生。GCN2基因的产物对于GCN4的翻译抑制是必不可少的。对GNC2基因的序列分析表明，GCN2蛋白具有一个与所有已知蛋白激酶的催化结构域高度同源的结构域。此外，GCN2菌株缺乏与根据GCN2开放阅读框架推导出的计算分子量的蛋白质相对应的蛋白激酶活性。因此，GCN2很可能编码一个蛋白激酶，它可能直接参与Gcn4mRNA的翻译调控。当细胞在氨基酸饥饿介质中培养时，GCN2基因的转录增加。这种转录激活是由Gcn4蛋白介导的，它与GCN2基因的启动子区域结合。因此，这个系统受转录-翻译调节回路的调节，该回路由氨基酸饥饿激活。激活并不是简单地定量增加电路中任何一个已识别的分量的结果。
GCN4 protein mediates the transcriptional activation of amino acid biosynthetic genes in Saccharomyces cerevisiae by specifically binding to DNA sequences in their 5''-regulatory regions. GCN4 expression is regulated at the level of translation, with translational derepression occurring under conditions of amino acid starvation. The product of the GCN2 gene is essential for translational depression of GCN4. Sequence analysis of the GNC2 gene reveals that the GCN2 protein has a domain highly homolgous to the catalytic domain of all known protein kinases. Furthermore, gcn2 strains are deficient in a protein kinase activity corresponding to a protein with the calculated molecular weight deduced from the GCN2 open reading frame. Therefore it is likely that GCN2 encodes a protein kinase, which may be directly involved in translational regulation of the GCN4 mRNA. Transcription of the GCN2 gene is increased when cells are cultured in amino acid starvation medium. This transcriptional activation is mediated by the GCN4 protein, which binds to the promoter region of the GCN2 gene. Thus, this system is modulated by a transcriptional-translational regulatory circuit, which is activated by amino acid starvation. Activation is not the result of a simple quantitative increase of either one of the identified components of the circuit.