Sch9 regulates ribosome biogenesis via Stb3, Dot6 and Tod6 and the histone deacetylase complex RPD3L
Sch9 regulates ribosome biogenesis via Stb3, Dot6 and Tod6 and the histone deacetylase complex RPD3L
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DOI：
10.1038/emboj.2011.221
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发表时间：
2011-08-03
期刊：
影响因子：
11.4
通讯作者：
Loewith, Robbie
中科院分区：
文献类型：
--
作者：
Huber, Alexandre;French, Sarah L.;Loewith, Robbie
TORC 1是一种保守的多亚基激酶复合物，调节真核生物生长的许多方面，包括核糖体的生物合成。驻留在TORC 1中的TOR蛋白激酶对环境信号有反应，并被天然产物雷帕霉素有效抑制。最近对酵母中雷帕霉素敏感的磷酸化蛋白质组的表征使人们对TORC 1如何调节生长有了深入的了解。在这里，我们表明，Sch 9，AGC家族激酶和直接底物的TORC 1，促进核糖体生物合成（Ribi）和核糖体蛋白（RP）基因的表达，通过直接抑制磷酸化的转录阻遏物Stb 3，Dot 6和Tod 6。STB 3、DOT 6和TOD 6的缺失部分绕过了sch 9菌株的生长和细胞大小缺陷，并揭示了Ribi和RP基因表达以及Ribi其他方面的相互依赖调节。Stb 3、Dot 6和Tod 6的去磷酸化使得能够募集RPD 3L组蛋白去乙酰化酶复合物以抑制Ribi/RP基因启动子。结合以往的研究，这些结果表明，Sch 9是核糖体生物合成的主调节因子，通过控制Ribi，RP，核糖体RNA和tRNA基因的转录。The EMBO Journal（2011）30，3052-3064. doi：10.1038/doj.2011.221; 2011年7月5日在线发布
TORC1 is a conserved multisubunit kinase complex that regulates many aspects of eukaryotic growth including the biosynthesis of ribosomes. The TOR protein kinase resident in TORC1 is responsive to environmental cues and is potently inhibited by the natural product rapamycin. Recent characterization of the rapamycin-sensitive phosphoproteome in yeast has yielded insights into how TORC1 regulates growth. Here, we show that Sch9, an AGC family kinase and direct substrate of TORC1, promotes ribosome biogenesis (Ribi) and ribosomal protein (RP) gene expression via direct inhibitory phosphorylation of the transcriptional repressors Stb3, Dot6 and Tod6. Deletion of STB3, DOT6 and TOD6 partially bypasses the growth and cell size defects of an sch9 strain and reveals interdependent regulation of both Ribi and RP gene expression, and other aspects of Ribi. Dephosphorylation of Stb3, Dot6 and Tod6 enables recruitment of the RPD3L histone deacetylase complex to repress Ribi/RP gene promoters. Taken together with previous studies, these results suggest that Sch9 is a master regulator of ribosome biogenesis through the control of Ribi, RP, ribosomal RNA and tRNA gene transcription. The EMBO Journal (2011) 30, 3052-3064. doi:10.1038/emboj.2011.221; Published online 5 July 2011