Epe1 contributes to activation of AMPK by promoting phosphorylation of AMPK alpha subunit, Ssp2.
Epe1 contributes to activation of AMPK by promoting phosphorylation of AMPK alpha subunit, Ssp2.
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Epe1 通过促进 AMPK α 亚基 Ssp2 的磷酸化来激活 AMPK。
DOI：
10.1038/s41598-017-03442-0
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发表时间：
2017
影响因子：
4.6
通讯作者：
Lu,Hong
中科院分区：
文献类型：
--
作者：
Chen,Yongyi;Hu,Xiaoyue;Guo,Chao;Yu,Yao;Lu,Hong
AMP 激活蛋白激酶 (AMPK) 是一种关键的细胞能量传感器。它被导致能量消耗的压力激活，并通过调节新陈代谢平衡启动适应性反应。 AMPK 形成 αβγ 异源三聚体。在裂殖酵母中，AMPK的激活主要依赖于上游激酶Ssp1对AMPKα亚基Ssp2 Thr189位点的磷酸化。然而，人们对这一过程的监管知之甚少。在这项研究中，我们确定 Epe1 是 AMPK 的新型正调节因子。 Epe1 是一种含有 jmjC 结构域的蛋白质，作为异染色质扩散的负调节因子而闻名。尽管 Epe1 在 AMPK 调节中的新作用依赖于 jmjC 结构域内预测的铁和 2-羟基戊二酸结合残基，但它似乎与异染色质扩散的抑制无关。 Epe1 直接与 Ssp2 相关，并在各种环境应激（包括低葡萄糖、高钠、高 pH 值和氧化条件）下促进 Ssp2 磷酸化。与 Epe1 类似，Jmj1 和 Msc1 也有助于 Ssp2 的磷酸化。 epe1+ 的缺失会损害 Ssp2 磷酸化后的下游事件，包括 Ssp2 的核转位、性分化和脂肪酸合成的抑制。我们的研究揭示了一种新的方法，其中含有 jmjC 结构域的蛋白质通过直接与主要传感器结合来调节适应性反应。
AMP-activated protein kinase (AMPK) is a pivotal cellular energy sensor. It is activated by stresses that cause depletion of energy and initiates adaptive responses by regulating metabolism balance. AMPK forms αβγ heterotrimer. In fission yeast, activation of AMPK mainly depends on the phosphorylation of AMPKα subunit Ssp2 at Thr189by upstream kinase Ssp1. However, not much is known about the regulation of this process. In this study, we identified Epe1 as a novel positive regulator of AMPK. Epe1, a jmjC-domain-containing protein, is best-known as a negative regulator of heterochromatin spreading. Although the novel role of Epe1 in regulation of AMPK relies on predicted iron- and 2-oxyglutarate-binding residues inside jmjC domain, it seems to be irrelevant to inhibition of heterochromatin spreading. Epe1 is associated with Ssp2 directly and promotes phosphorylation of Ssp2 upon various environmental stresses, including low-glucose, high-sodium, high-pH and oxidative conditions. Similar to Epe1, Jmj1 and Msc1 also contribute to phosphorylation of Ssp2. Deletion ofepe1+impairs downstream events following phosphorylation of Ssp2, including nuclear translocation of Ssp2, sexual differentiation and inhibition of fatty acid synthesis. Our study reveals a novel way in which a jmjC-domain-containing protein regulates adaptive response by directly binding to a principal sensor.