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Lee J.-M.,National Creative Research Initiatives Center | Lee J.-M.,Chonnam National University | Gang G.-T.,Korea Research Institute of Bioscience and Biotechnology | Kim D.-K.,National Creative Research Initiatives Center | And 7 more authors.
Journal of Biological Chemistry | Year: 2014

Background: Small heterodimer partner interacting leucine zipper protein (SMILE) is a nuclear corepressor of the nuclear receptor family. Results: Ursodeoxycholic acid (UDCA) increases SMILE gene expression, which contributes to inhibiting liver X receptor α (LXRα)-mediated hepatic lipogenesis. Conclusion: UDCA-induced smile inhibits LXRα-mediated hepatic lipogenic gene expression. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.


Shao D.,Cardiovascular Research Institute | Zhai P.,Cardiovascular Research Institute | Del Re D.P.,Cardiovascular Research Institute | Sciarretta S.,Cardiovascular Research Institute | And 5 more authors.
Nature Communications | Year: 2014

The Hippo pathway is an evolutionarily conserved regulator of organ size and tumorigenesis that negatively regulates cell growth and survival. Here we report that Yes-associated protein (YAP), the terminal effector of the Hippo pathway, interacts with FoxO1 in the nucleus of cardiomyocytes, thereby promoting survival. YAP and FoxO1 form a functional complex on the promoters of the catalase and manganese superoxide dismutase (MnSOD) antioxidant genes and stimulate their transcription. Inactivation of YAP, induced by Hippo activation, suppresses FoxO1 activity and decreases antioxidant gene expression, suggesting that Hippo signalling modulates the FoxO1-mediated antioxidant response. In the setting of ischaemia/reperfusion (I/R) in the heart, activation of Hippo antagonizes YAP-FoxO1, leading to enhanced oxidative stress-induced cell death through downregulation of catalase and MnSOD. Conversely, restoration of YAP activity protects against I/R injury. These results suggest that YAP is a nuclear co-factor of FoxO1 and that the Hippo pathway negatively affects cardiomyocyte survival by inhibiting the function of YAP-FoxO1. © 2014 Macmillan Publishers Limited.

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