Roussou I, Thireos G, Hauge B M
University of Crete, Department of Biology, Greece.
Mol Cell Biol. 1988 May;8(5):2132-9. doi: 10.1128/mcb.8.5.2132-2139.1988.
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 derepression of GCN4. Sequence analysis of the GCN2 gene reveals that the GCN2 protein has a domain highly homologous 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.
GCN4蛋白通过特异性结合酿酒酵母中氨基酸生物合成基因5'-调控区的DNA序列，介导这些基因的转录激活。GCN4的表达在翻译水平受到调控，在氨基酸饥饿条件下会发生翻译去抑制。GCN2基因的产物对于GCN4的翻译去抑制至关重要。对GCN2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菌株缺乏一种与根据GCN2开放阅读框推导的计算分子量的蛋白质相对应的蛋白激酶活性。因此，GCN2可能编码一种蛋白激酶，它可能直接参与GCN4 mRNA的翻译调控。当细胞在氨基酸饥饿培养基中培养时，GCN2基因的转录会增加。这种转录激活由GCN4蛋白介导，GCN4蛋白与GCN2基因的启动子区域结合。因此，该系统由一个转录-翻译调控回路调节，该回路由氨基酸饥饿激活。激活不是回路中任何一个已鉴定成分简单定量增加的结果。
