Ivanov M S, Radchenko E A, Mironova L N
Mol Biol (Mosk). 2010 Nov-Dec;44(6):1018-26.
It is known that nonsense suppression efficiency in yeast is controlled both genetically and epigenetically. As many components of translation machinery are represented by phosphoproteins, it depends, in particular, on the activity of kinases and phosphatases. The Ppz1p/Hal3p complex is among them. In this complex, the Ppz1p phosphatase is a catalytic subunit and Hal3p negatively regulates its function. The aim of this work was to study mechanisms which relate the activity of Ppz1p/Hal3p complex to nonsense suppression efficiency. In this study we used a genetic approach consisting of the analysis of nonsense suppression phenotype of strains over-expressing HAL3 or PPZ1 genes and also bearing deletions or mutant alleles of genes which presumably could participate in the manifestation of these over-expressions. We have shown that Hal3p inhibits not only Ppz1p, but also the homologous phosphatase Ppz2p. Our data indicate that Ppz2p is also involved in the control of nonsense suppression efficiency. In the course of search for Ppz1p target protein, it was shown that Ppz1p dephosphorylates at least two proteins participating in translation. Moreover, Ppz1p affects nonsense suppression efficiency not only due to its phosphatase activity but also due to another mechanism triggered by its interaction with Hsp70 chaperones.
已知酵母中的无义抑制效率受遗传和表观遗传控制。由于翻译机制的许多成分由磷蛋白代表，它尤其取决于激酶和磷酸酶的活性。Ppz1p/Hal3p复合物就是其中之一。在这个复合物中，Ppz1p磷酸酶是催化亚基，而Hal3p负向调节其功能。这项工作的目的是研究将Ppz1p/Hal3p复合物的活性与无义抑制效率联系起来的机制。在本研究中，我们使用了一种遗传方法，包括分析过表达HAL3或PPZ1基因的菌株的无义抑制表型，以及携带可能参与这些过表达表现的基因缺失或突变等位基因的菌株。我们已经表明，Hal3p不仅抑制Ppz1p，还抑制同源磷酸酶Ppz2p。我们的数据表明，Ppz2p也参与无义抑制效率的控制。在寻找Ppz1p靶蛋白的过程中，发现Ppz1p使至少两种参与翻译的蛋白去磷酸化。此外，Ppz1p影响无义抑制效率不仅是由于其磷酸酶活性，还由于其与Hsp70伴侣相互作用触发的另一种机制。
