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首页> 外文期刊>Molecular biology of the cell >DNA binding by the MATα2 transcription factor controls its access to alternative ubiquitin-modification pathways
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DNA binding by the MATα2 transcription factor controls its access to alternative ubiquitin-modification pathways

机译：通过Matα2转录因子的DNA结合控制其对替代泛素改性途径的访问

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Like many transcription factors, the yeast protein MATalpha2 (α2) undergoes rapid proteolysis via the ubiquitin-proteasome system (UPS). At least two ubiquitylation pathways regulate α2 degradation: one pathway utilizes the ubiquitin ligase (E3) Doa10 and the other the heterodimeric E3 Slx5/Slx8. Doa10 is a transmembrane protein of the endoplasmic reticulum/inner nuclear membrane, whereas Slx5/Slx8 localizes to the nucleus and binds DNA nonspecifically. While a single protein can often be ubiquitylated by multiple pathways, the reasons for this “division of labor” are not well understood. Here we show that α2 mutants with impaired DNA binding become inaccessible to the Slx5/Slx8 pathway but are still rapidly degraded through efficient shunting to the Doa10 pathway. These results are consistent with the distinct localization of these E3s. We also characterized a novel class of DNA binding-defective α2 variants whose degradation is strongly impaired. Our genetic data suggest that this is due to a gain-of-function interaction that limits their access to Doa10. Together, these results suggest multiple ubiquitin-ligation mechanisms may have evolved to promote rapid destruction of a transcription factor that resides in distinct cellular subcompartments under different conditions. Moreover, gain-of-function mutations, which also occur with oncogenic forms of human transcription factors such as p53, may derail this fail-safe system.
机译：与许多转录因子一样，酵母蛋白质matalpha2（α2）通过遍突蛋白 - 蛋白酶体系（UPS）进行快速蛋白水解。至少两种ubiquitylation途径调节α2降解：一种途径利用泛素连接酶（E3）DOA10和其它异二聚体E3 SLX5 / SLX8。 DOA10是内质网/内核膜的跨膜蛋白，而SLX5 / SLX8定位于细胞核并非特异性地结合DNA。虽然单一蛋白质通常可以通过多种途径繁多，但是这种“劳动划分”的原因并不充分了解。在这里，我们显示DNA结合受损的α2突变体对SLX5 / SLX8通路无法进入，但通过有效分流仍然迅速降低到DOA10途径。这些结果与这些E3s的不同定位一致。我们还表征了一种新型的DNA结合缺陷α2变体，其降解受到强烈损害。我们的遗传数据表明，这是由于功能的互动互动，这限制了他们对DOA10的访问。这些结果表明多种泛素连接机制可能已经进化以促进在不同条件下促进在不同细胞子组件中的转录因子的快速破坏。此外，还发生了功能性突变，其致癌形式的人转录因子如p53，可能会剥夺这种故障安全系统。

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