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Insulin suppresses transcriptional activity of yes-associated protein in insulin target cells

Samar Sayedyahossein1, Andrew C Hedman1, David B Sacks1

  • 1Department of Laboratory Medicine, National Institutes of Health, Bethesda, MD 20892.

Molecular Biology of the Cell
|November 7, 2019
PubMed

Insights

Insulin suppresses the activity of Yes-associated protein (YAP), a key Hippo pathway coactivator, in liver and muscle cells. This finding reveals new insights into insulin and Hippo pathway cross-talk.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Endocrinology

Background:

  • Yes-associated protein (YAP) is a transcriptional coactivator in the Hippo pathway, involved in cellular nutrient and energy regulation.
  • The precise mechanisms by which YAP controls these cellular states are not fully understood.

Purpose of the Study:

  • To investigate the role of insulin in modulating YAP activity.
  • To elucidate the cross-talk between the insulin and Hippo pathways.

Main Methods:

  • Insulin treatment of HepG2 and C2C12 cells.
  • Analysis of YAP phosphorylation and nuclear abundance.
  • Proximity ligation assay to assess YAP-TEAD interactions.
  • Measurement of YAP/TEAD-mediated transcription and target gene expression.
  • Experiments in YAP-deficient cells and under serum starvation conditions.

Main Results:

  • Insulin treatment decreased YAP nuclear abundance and YAP-TEAD interactions in HepG2 cells.
  • Insulin inhibited YAP/TEAD-mediated transcription and YAP target gene expression in HepG2 and C2C12 cells.
  • Serum starvation reversed insulin's effects on YAP phosphorylation and transcription.
  • YAP deficiency attenuated insulin's inhibitory effect on gluconeogenesis genes (G6PC, PCK1).

Conclusions:

  • Insulin acts as a suppressor of YAP activity in insulin target cells.
  • This study reveals a novel cross-talk mechanism between the insulin and Hippo signaling pathways.

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