Integration of Multiple Nutrient Cues and Regulation of Lifespan by Ribosomal Transcription Factor Ifh1
Integration of Multiple Nutrient Cues and Regulation of Lifespan by Ribosomal Transcription Factor Ifh1
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DOI：
10.1016/j.celrep.2013.08.016
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发表时间：
2013-09-01
期刊：
影响因子：
8.8
通讯作者：
Tu, Benjamin P.
中科院分区：
文献类型：
--
作者：
Cai, Ling;McCormick, Mark A.;Tu, Benjamin P.
核糖体生物合成需要在生长细胞中投入大量的能量和资源。在芽殖酵母中，转录辅激活因子Ifh 1 p是核糖体蛋白（RP）基因转录的重要调节因子。在这里，我们报告说，Ifh 1 p是动态乙酰化和磷酸化作为细胞生长状态的函数。Ifh 1 p在其N-末端区域的许多位点被Gcn 5 p乙酰化，并被沉默调节蛋白家族的NAD（+）依赖性脱乙酰酶脱乙酰化。Ifh 1 p的乙酰化反应于细胞内乙酰辅酶A水平，并用于调节Ifh 1 p的稳定性。Ifh 1 p的磷酸化由蛋白激酶A介导，并依赖于TORC 1信号。因此，多种营养感应机制汇聚在Ifh 1 p上。然而，而不是调节RP基因转录或细胞生长的总体速率，Ifh 1 p的营养响应磷酸化在细胞复制寿命的调节中起着更突出的作用。
Ribosome biogenesis requires an enormous commitment of energy and resources in growing cells. In budding yeast, the transcriptional coactivator Ifh1p is an essential regulator of ribosomal protein (RP) gene transcription. Here, we report that Ifh1p is dynamically acetylated and phosphorylated as a function of the growth state of cells. Ifh1p is acetylated at numerous sites in its N-terminal region by Gcn5p and deacetylated by NAD(+)-dependent deacetylases of the sirtuin family. Acetylation of Ifh1p is responsive to intracellular acetyl-CoA levels and serves to regulate the stability of Ifh1p. The phosphorylation of Ifh1p is mediated by protein kinase A and is dependent on TORC1 signaling. Thus, multiple nutrient-sensing mechanisms converge on Ifh1p. However, instead of modulating overall rates of RP gene transcription or cell growth, the nutrient-responsive phosphorylation of Ifh1p plays a more prominent role in the regulation of cellular replicative lifespan.