Tzamarias D, Struhl K
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Genes Dev. 1995 Apr 1;9(7):821-31. doi: 10.1101/gad.9.7.821.
The yeast Cyc8(Ssn6)-Tup1 complex is required for transcriptional repression of distinct sets of genes that are regulated by glucose, oxygen, cell type, and DNA damage. It has been proposed that the Cyc8-Tup1 complex is a corepressor that is recruited to promoters by interacting with pathway-specific DNA-binding proteins. Previously, we showed that a specific region of Tup1 mediates the general transcriptional repression function of the complex. Here, we define functional domains of Cyc8, a protein consisting primarily of 10 tandem copies of a TPR motif. Distinct combinations of TPR motifs are required specifically for direct interaction with Tup1, repression of oxygen-regulated genes, and repression of glucose-regulated genes. In contrast, the WD motifs of Tup1 are not essential for repression of genes regulated by glucose and oxygen, but they are required for those regulated by cell type and DNA damage. In addition, we show that the Cyc8-Tup1 complex functions both as a corepressor and an inhibitor of Mig1, a protein that binds to promoters of glucose-repressible genes. These observations suggest that different Cyc8 TPR motifs and the Tup1 WD domain mediate distinct protein-protein interactions that link the Cyc8-Tup1 corepressor to structurally dissimilar DNA-binding proteins required for pathway-specific regulation.
酵母Cyc8（Ssn6）-Tup1复合物对于由葡萄糖、氧气、细胞类型和DNA损伤所调控的不同基因集的转录抑制是必需的。有人提出，Cyc8-Tup1复合物是一种共抑制因子，它通过与途径特异性DNA结合蛋白相互作用而被招募到启动子上。此前，我们表明Tup1的一个特定区域介导了该复合物的一般转录抑制功能。在此，我们定义了Cyc8的功能结构域，Cyc8是一种主要由10个TPR基序串联拷贝组成的蛋白质。TPR基序的不同组合分别是与Tup1直接相互作用、抑制氧气调控基因以及抑制葡萄糖调控基因所必需的。相比之下，Tup1的WD基序对于葡萄糖和氧气调控基因的抑制并非必需，但对于细胞类型和DNA损伤所调控的基因抑制却是必需的。此外，我们表明Cyc8-Tup1复合物既作为共抑制因子发挥作用，又作为Mig1的抑制剂发挥作用，Mig1是一种与葡萄糖可抑制基因启动子结合的蛋白质。这些观察结果表明，不同的Cyc8 TPR基序和Tup1 WD结构域介导了不同的蛋白质-蛋白质相互作用，这些相互作用将Cyc8-Tup1共抑制因子与途径特异性调控所需的结构不同的DNA结合蛋白联系起来。
