Research ArticleMetabolism

Transcriptional activation of lipogenesis by insulin requires phosphorylation of MED17 by CK2

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Science Signaling  21 Feb 2017:
Vol. 10, Issue 467, eaai8596
DOI: 10.1126/scisignal.aai8596

Linking insulin to lipogenesis through MED17

Food intake stimulates the release of insulin, which triggers various anabolic processes including lipogenesis in the liver. Viscarra et al. found that insulin stimulation in hepatocytes or feeding in mice triggered the phosphorylation of the transcriptional coactivator MED17, which enabled the transcription factor USF1 to activate genes encoding lipogenic factors. This phosphorylation event, which was mediated by the kinase CK2, occurred only if MED17 was not previously phosphorylated by p38, a kinase that is activated by fasting. Knockdown of CK2 or administration of a CK2 inhibitor reduced lipogenesis and triglyceride content in the livers of mice. Inappropriate accumulation of fatty acids in the liver, a condition called hepatic steatosis, can lead to hepatic dysfunction and cancer, suggesting that CK2 or other components in this pathway could be targeted to prevent this common metabolic condition.

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