PLK1 (polo like kinase 1) inhibits MTOR complex 1 and promotes autophagy.

摘要: ABSTRACTMechanistic target of rapamycin complex 1 (MTORC1) and polo like kinase (PLK1) are major drivers cancer cell growth proliferation, inhibitors both protein kinases currently being investigated in clinical studies. To date, MTORC1′s PLK1′s functions mostly studied separately, reports on their mutual crosstalk scarce. Here, we identify PLK1 as a physical MTORC1 interactor human cells. inhibition enhances activity under nutrient sufficiency starved cells, directly phosphorylates the component RPTOR/RAPTOR vitro. reside together at lysosomes, subcellular site where is active. Consistent with an inhibitory role toward MTORC1, overexpression inhibits lysosomal association PLK1-MTORC1 complex, whereas promotes localization MTOR. binding enhanced by amino acid starvation, condition known to increase autophagy. a...