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 rema...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 sub- strate KIF4A is phosphorylated by AMPK at Set801. Further analysis revealed that AMPK and Aurora B competitively phosphore- gulates KIF4A during mitotic phase due to overlapping recognition motifs, resulting in the elaborate phosphoregutation 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.展开更多
基金This work was supported by the National Natural Science Foundation of China （81673489）, the State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences （SIMM1705ZZ-02）, Institutes for Drug Discovery and Development, Chinese Academy of Sciences （CASIMM0120161001）, and the Science and Technology Commission of Shanghai Municipality （16430724100 and 14431902800）.
文摘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 sub- strate KIF4A is phosphorylated by AMPK at Set801. Further analysis revealed that AMPK and Aurora B competitively phosphore- gulates KIF4A during mitotic phase due to overlapping recognition motifs, resulting in the elaborate phosphoregutation 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.
