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Heat Shock Factor 1 Is a Direct Antagonist of AMP-Activated Protein Kinase

Mol Cell.. 2019; 
Su KH1, Dai S2, Tang Z3, Xu M1, Dai C4.
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摘要

Through transcriptional control of the evolutionarily conserved heat shock, or proteotoxic stress, response, heat shock factor 1 (HSF1) preserves proteomic stability. Here, we show that HSF1, a physiological substrate for AMP-activated protein kinase (AMPK), constitutively suppresses this central metabolic sensor. By physically evoking conformational switching of AMPK, HSF1 impairs AMP binding to the γ subunits and enhances the PP2A-mediated de-phosphorylation, but it impedes the LKB1-mediated phosphorylation of Thr172, and retards ATP binding to the catalytic α subunits. These immediate and manifold regulations empower HSF1 to both repress AMPK under basal conditions and restrain its activation by diverse st... More

关键词

AMPK; HSF1; LKB1; SHH; SREBP1; cholesteroylation; conformational switch; lipogenesis; oncogenesis