A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress
A Critical SUMO1 Modification of LKB1 Regulates AMPK Activity during Energy Stress
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DOI：
10.1016/j.celrep.2015.07.002
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发表时间：
2015-08-04
期刊：
影响因子：
8.8
通讯作者：
Yeh, Edward T. H.
中科院分区：
文献类型：
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作者：
Ritho, Joan;Arold, Stefan T.;Yeh, Edward T. H.
SUMO化与细胞应激适应有关，但其在调节肝激酶B1（LKB 1）（能量传感器AMP活化蛋白激酶（AMPK）的主要上游激酶）中的作用尚不清楚。在这里，我们表明，能量应激触发增加SUMO 1修饰LKB 1，尽管在SUMO 1和SUMO 2/3共轭物的整体减少。在代谢应激过程中，LKB 1赖氨酸178的SUMO 1修饰在促进其与AMPK通过AMPK活化所必需的SUMO相互作用基序（SIM）相互作用方面至关重要。LKB 1 K178 R SUMO突变体具有缺陷的AMPK信号传导和线粒体功能，诱导能量剥夺细胞死亡。这些结果为能量应激期间LKB 1-AMPK信号传导如何调节提供了额外的见解，并强调了SUMO化在维持细胞能量平衡方面的关键作用。
SUMOylation has been implicated in cellular stress adaptation, but its role in regulating liver kinase B1 (LKB1), a major upstream kinase of the energy sensor AMP-activated protein kinase (AMPK), is unknown. Here, we show that energy stress triggers an increase in SUMO1 modification of LKB1, despite a global reduction in both SUMO1 and SUMO2/3 conjugates. During metabolic stress, SUMO1 modification of LKB1 lysine 178 is essential in promoting its interaction with AMPK via a SUMO-interacting motif (SIM) essential for AMPK activation. The LKB1 K178R SUMO mutant had defective AMPK signaling and mitochondrial function, inducing death in energy-deprived cells. These results provide additional insight into how LKB1-AMPK signaling is regulated during energy stress, and they highlight the critical role of SUMOylation in maintaining the cell's energy equilibrium.