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Englerin A stimulates PKC? to inhibit insulin signaling and to simultaneously activate HSF1: pharmacologically induced synthetic lethality.

ABSTRACT: The natural product englerin A (EA) binds to and activates protein kinase C-? (PKC?). EA-dependent activation of PKC? induces an insulin-resistant phenotype, limiting the access of tumor cells to glucose. At the same time, EA causes PKC?-mediated phosphorylation and activation of the transcription factor heat shock factor 1, an inducer of glucose dependence. By promoting glucose addiction, while simultaneously starving cells of glucose, EA proves to be synthetically lethal to highly glycolytic tumors.

SUBMITTER: Sourbier C

PROVIDER: S-EPMC3574184 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Englerin A stimulates PKCθ to inhibit insulin signaling and to simultaneously activate HSF1: pharmacologically induced synthetic lethality.

Sourbier Carole C Scroggins Bradley T BT Ratnayake Ranjala R Prince Thomas L TL Lee Sunmin S Lee Min-Jung MJ Nagy Peter Literati PL Lee Young H YH Trepel Jane B JB Beutler John A JA Linehan W Marston WM Neckers Len L

Cancer cell 20130123 2

The natural product englerin A (EA) binds to and activates protein kinase C-θ (PKCθ). EA-dependent activation of PKCθ induces an insulin-resistant phenotype, limiting the access of tumor cells to glucose. At the same time, EA causes PKCθ-mediated phosphorylation and activation of the transcription factor heat shock factor 1, an inducer of glucose dependence. By promoting glucose addiction, while simultaneously starving cells of glucose, EA proves to be synthetically lethal to highly glycolytic t ...[more]

PMID: 23352416

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