Hoppe Sven, Bierhoff Holger, Cado Ivana, Weber Andrea, Tiebe Marcel, Grummt Ingrid, Voit Renate
Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, INF 581, D-69120 Heidelberg, Germany.
Proc Natl Acad Sci U S A. 2009 Oct 20;106(42):17781-6. doi: 10.1073/pnas.0909873106. Epub 2009 Oct 6.
AMP-activated protein kinase (AMPK) senses changes in the intracellular AMP/ATP ratio, switching off energy-consuming processes and switching on catabolic pathways in response to energy depletion. Here, we show that AMPK down-regulates rRNA synthesis under glucose restriction by phosphorylating the RNA polymerase I (Pol I)-associated transcription factor TIF-IA at a single serine residue (Ser-635). Phosphorylation by AMPK impairs the interaction of TIF-IA with the TBP-containing promoter selectivity factor SL1, thereby precluding the assembly of functional transcription initiation complexes. Mutation of Ser-635 compromises down-regulation of Pol I transcription in response to low energy supply, supporting that activation of AMPK adapts rRNA synthesis to nutrient availability and the cellular energy status.
AMP 激活的蛋白激酶（AMPK）可感知细胞内 AMP/ATP 比值的变化，在能量耗竭时关闭耗能过程并开启分解代谢途径。在此，我们表明，在葡萄糖限制条件下，AMPK 通过磷酸化与 RNA 聚合酶 I（Pol I）相关的转录因子 TIF-IA 的单个丝氨酸残基（Ser-635）来下调 rRNA 的合成。AMPK 介导的磷酸化会损害 TIF-IA 与含 TBP 的启动子选择性因子 SL1 的相互作用，从而阻止功能性转录起始复合物的组装。Ser-635 的突变会损害低能量供应时 Pol I 转录的下调，这支持了 AMPK 的激活使 rRNA 合成适应营养可用性和细胞能量状态。
