MULTIPLE GCD GENES REQUIRED FOR REPRESSION OF GCN4, A TRANSCRIPTIONAL ACTIVATOR OF AMINO-ACID BIOSYNTHETIC GENES IN SACCHAROMYCES-CEREVISIAE
MULTIPLE GCD GENES REQUIRED FOR REPRESSION OF GCN4, A TRANSCRIPTIONAL ACTIVATOR OF AMINO-ACID BIOSYNTHETIC GENES IN SACCHAROMYCES-CEREVISIAE
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DOI：
10.1128/mcb.6.11.3990
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发表时间：
1986-11-01
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：
HARASHIMA, S;HINNEBUSCH, AG
GCN 4编码酿酒酵母中编码氨基酸生物合成酶的多个非连锁基因的正调控因子。GCN 4的表达通过一种控制机制与氨基酸可用性偶联，该控制机制涉及GCD 1作为GCN 4表达的负效应物，GCN 1、GCN 2和GCN 3作为GCN 4表达的正效应物。我们使用gcn2 gcn3双突变的回复来分离GCD 1的新等位基因和另外四个GCD基因中的突变，我们将其命名为GCD 10、GCD 11、GCD 12和GCD 13。在不存在GCN 2+和GCN 3+等位基因的情况下，所有突变都会导致HIS 4转录的组成性去抑制。相比之下，gcd突变需要野生型GCN 4等位基因才能发挥去抑制作用，这表明每个突变都是通过影响细胞中GCN 4活性水平来发挥作用的。与这种解释一致，每个GCD基因中的突变导致GCN 4：：lacZ基因融合的组成性去阻遏。因此，在非饥饿条件下，至少需要五种基因产物来维持GCN 4表达的正常抑制水平。有趣的是，gcd突变是多效性的，并且在非饥饿条件下也影响生长速率。此外，某些等位基因导致杀伤表型所需的M双链RNA的丢失。这种多效性表明，GCD基因产物有助于一个基本的细胞功能，除了，或结合，他们在GCN 4调节的作用。
GCN4 encodes a positive regulator of multiple unlinked genes encoding amino acid biosynthetic enzymes in Saccharomyces cerevisiae. Expression of GCN4 is coupled to amino acid availability by a control mechanism involving GCD1 as a negative effector and GCN1, GCN2, and GCN3 as positive effectors of GCN4 expression. We used reversion of a gcn2 gcn3 double mutation to isolate new alleles of GCD1 and mutations in four additional GCD genes which we designate GCD10, GCD11, GCD12, and GCD13. All of the mutations lead to constitutive derepression of HIS4 transcription in the absence of the GCN2+ and GCN3+ alleles. By contrast, the gcd mutations require the wild-type GCN4 allele for their derepressing effect, suggesting that each acts by influencing the level of GCN4 activity in the cell. Consistent with this interpretation, mutations in each GCD gene lead to constitutive derepression of a GCN4::lacZ gene fusion. Thus, at least five gene products are required to maintain the normal repressed level of GCN4 expression in nonstarvation conditions. Interestingly, the gcd mutations are pleiotropic and also affect growth rate in nonstarvation conditions. In addition, certain alleles lead to a loss of M double-stranded RNA required for the the killer phenotype. This pleiotropy suggests that the GCD gene products contribute to an essential cellular function, in addition to, or in conjunction with, their role in GCN4 regulation.