Boban Mirta, Zargari Arezou, Andréasson Claes, Heessen Stijn, Thyberg Johan, Ljungdahl Per O
Ludwig Institute for Cancer Research, S-171 77 Stockholm, Sweden.
J Cell Biol. 2006 Jun 5;173(5):695-707. doi: 10.1083/jcb.200601011. Epub 2006 May 30.
Stp1 and Stp2 are homologous transcription factors in yeast that are synthesized as latent cytoplasmic precursors with NH2-terminal regulatory domains. In response to extracellular amino acids, the plasma membrane-localized Ssy1-Ptr3-Ssy5 (SPS) sensor endoproteolytically processes Stp1 and Stp2, an event that releases the regulatory domains. The processed forms of Stp1 and Stp2 efficiently target to the nucleus and bind promoters of amino acid permease genes. In this study, we report that Asi1 is an integral component of the inner nuclear membrane that maintains the latent characteristics of unprocessed Stp1 and Stp2. In cells lacking Asi1, full-length forms of Stp1 and Stp2 constitutively induce SPS sensor-regulated genes. The regulatory domains of Stp1 and Stp2 contain a conserved motif that confers Asi1-mediated control when fused to an unrelated DNA-binding protein. Our results indicate that latent precursor forms of Stp1 and Stp2 inefficiently enter the nucleus; however, once there, Asi1 restricts them from binding SPS sensor-regulated promoters. These findings reveal an unanticipated role of inner nuclear membrane proteins in controlling gene expression.
Stp1和Stp2是酵母中的同源转录因子，它们作为具有NH2末端调节结构域的潜在细胞质前体被合成。响应细胞外氨基酸，定位于质膜的Ssy1-Ptr3-Ssy5（SPS）传感器对内切蛋白水解处理Stp1和Stp2，这一事件释放调节结构域。Stp1和Stp2的加工形式有效地靶向细胞核并结合氨基酸通透酶基因的启动子。在本研究中，我们报道Asi1是内核膜的一个组成部分，它维持未加工的Stp1和Stp2的潜在特性。在缺乏Asi1的细胞中，Stp1和Stp2的全长形式组成性地诱导SPS传感器调节的基因。Stp1和Stp2的调节结构域包含一个保守基序，当与无关的DNA结合蛋白融合时，该基序赋予Asi1介导的控制。我们的结果表明，Stp1和Stp2的潜在前体形式低效地进入细胞核；然而，一旦进入细胞核，Asi1会限制它们结合SPS传感器调节的启动子。这些发现揭示了内核膜蛋白在控制基因表达中的意外作用。
