National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
J Mol Cell Biol. 2018 Feb 1;10(1):2-17. doi: 10.1093/jmcb/mjx029.
AMP-activated protein kinase (AMPK) is an energy sensor that couples the cellular energy state with basic biological processes. AMPK is thought to be linked with cell division although the underlying mechanisms remain largely unknown. Here, we show that AMPK functionally participates throughout cell division and that AMPK catalytic subunits, especially α2, are sequentially associated with separate mitotic apparatus. Using quantitative phosphoproteomics analysis, we found that the strong direct substrate KIF4A is phosphorylated by AMPK at Ser801. Further analysis revealed that AMPK and Aurora B competitively phosphoregulates KIF4A during mitotic phase due to overlapping recognition motifs, resulting in the elaborate phosphoregulation for KIF4A-dependent central spindle length control. Given the intrinsic energy-sensing function of AMPK, our study links the KIF4A-dependent control of central spindle length with cellular glucose stress.
AMP 激活的蛋白激酶（AMPK）是一种能量传感器，它将细胞能量状态与基本的生物过程联系起来。尽管其潜在机制在很大程度上仍不清楚，但人们认为 AMPK 与细胞分裂有关。在这里，我们表明 AMPK 在整个细胞分裂过程中发挥功能，并且 AMPK 催化亚基，特别是α2，与独立的有丝分裂装置依次相关。使用定量磷酸蛋白质组学分析，我们发现强的直接底物 KIF4A 在 Ser801 处被 AMPK 磷酸化。进一步的分析表明，由于重叠的识别基序，AMPK 和 Aurora B 在有丝分裂期间竞争调节 KIF4A 的磷酸化，导致 KIF4A 依赖的中心纺锤体长度控制的精细磷酸化调节。鉴于 AMPK 的固有能量感应功能，我们的研究将 KIF4A 依赖的中心纺锤体长度控制与细胞葡萄糖应激联系起来。
