Intestinal tumorigenesis is a result of mutations in signaling pathways that control cellular proliferation, differentiation, and survival. Mutations in the Wnt/β-catenin pathway are associated with the majority of intestinal cancers, while dysregulation of the Hippo/Yes-Associated Protein (YAP) pathway is an emerging regulator of intestinal tumorigenesis. In addition, these closely related pathways play a central role during intestinal regeneration. We have previously shown that methylation of the Hippo transducer YAP by the lysine methyltransferase SETD7 controls its subcellular localization and function. We now show that SETD7 is required for Wnt-driven intestinal tumorigenesis and regeneration. Mechanistically, SETD7 is part of a complex containing YAP, AXIN1, and β-catenin, and SETD7-dependent methylation of YAP facilitates Wnt-induced nuclear accumulation of β-catenin. Collectively, these results define a methyltransferase-dependent regulatory mechanism that links the Wnt/β-catenin and Hippo/YAP pathways during intestinal regeneration and tumorigenesis.

Excess partial molar enthalpies of 1-propanol, H 1P E, in 1-propanol−NaCl−H2O were measured directly, accurately, and in small increments in mole fraction of 1-propanol, x 1P, at 25 °C in the range x NaCl < 0.04. x NaCl is the mole fraction of NaCl. The enthalpic interaction function, H 1P - 1P E, between 1-propanol molecules was then evaluated. H 1P - 1P E is a convenient, model-free measure for the intermolecular interaction in terms of enthalpy. The behavior of these thermodynamic quantities was compared with that of the binary 1-propanol−H2O. Based on the knowledge accumulated in our laboratory on the binary aqueous 1-propanol, the effect of NaCl on H2O became apparent. Our tentative conclusions are that (1) a NaCl molecule “binds” to seven or eight molecules of H2O on dissolving into H2O, and (2) the reminder of bulk H2O away from solute NaCl is not affected and stays almost the same as pure H2O.

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