AMP-activated protein kinase adapts rRNA synthesis to cellular energy supply
AMP-activated protein kinase adapts rRNA synthesis to cellular energy supply
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DOI：
10.1073/pnas.0909873106
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发表时间：
2009-10-20
影响因子：
11.1
通讯作者：
Voit, Renate
中科院分区：
文献类型：
--
作者：
Hoppe, Sven;Bierhoff, Holger;Voit, Renate
AMP激活的蛋白激酶（AMPK）感知细胞内AMP/ATP比率的变化，关闭能量消耗过程并打开分解代谢途径以响应能量消耗。在这里，我们表明，AMPK下调rRNA合成葡萄糖限制下磷酸化的RNA聚合酶I（Pol I）相关的转录因子TIF-IA在一个单一的丝氨酸残基（Ser-635）。AMPK的磷酸化损害了TIF-IA与含TBP的启动子选择性因子SL 1的相互作用，从而阻止了功能性转录起始复合物的组装。Ser-635突变导致Pol I转录响应于低能量供应而下调，这支持AMPK的激活使rRNA合成适应于营养可用性和细胞能量状态。
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.