Graduate Program in Cellular and Molecular Pharmacology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ, USA.
Cell Cycle. 2009 Dec 15;8(24):4085-90. doi: 10.4161/cc.8.24.10170. Epub 2009 Dec 25.
TORC1 is a central regulator of ribosomal RNA synthesis. Here we report that Sch9 partially mediates TORC1 signaling to regulate Pol I- and Pol III-dependent transcription. Mechanistically, Sch9 is involved in hyperphosphorylation and cytoplasmic localization of Maf1, and for optimal synthesis of rRNAs and tRNAs. Interestingly, sch9Delta does not affect Maf1 basal phosphorylation and nucleolar localization. In addition, TORC1 is still capable of regulating rRNAs and tRNAs in the absence of Sch9. Moreover, the hyperactive Sch9(2D3E) mutant does not confer significant rapamycin resistance in cell growth. Together, these observations indicate that Sch9 is involved in optimal regulation of ribosome biogenesis by TORC1, but is dispensable for the essential aspects of ribosome biogenesis and cell growth, suggesting that TORC1 controls cell growth through Sch9-dependent and independent mechanisms.
TORC1 是核糖体 RNA 合成的一个核心调节剂。在这里，我们报告说 Sch9 部分介导 TORC1 信号转导以调节 Pol I 和 Pol III 依赖性转录。从机制上讲，Sch9 参与了 Maf1 的过度磷酸化和细胞质定位，以及 rRNA 和 tRNA 的最佳合成。有趣的是，sch9Δ 并不影响 Maf1 的基础磷酸化和核仁定位。此外，在没有 Sch9 的情况下，TORC1 仍然能够调节 rRNA 和 tRNA。此外，高活性的 Sch9(2D3E)突变体在细胞生长中不会赋予显著的雷帕霉素抗性。综上所述，这些观察结果表明，Sch9 参与了 TORC1 对核糖体生物发生的最佳调节，但对于核糖体生物发生和细胞生长的基本方面是可有可无的，这表明 TORC1 通过 Sch9 依赖和独立的机制控制细胞生长。
