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Hepatology
Article
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Hepatology
Article . 2017 . Peer-reviewed
License: Wiley Online Library User Agreement
Data sources: Crossref
Hepatology
Article . 2017
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YAP suppresses gluconeogenic gene expression through PGC1α

Authors: Yue, Hu; Dong-Ju, Shin; Hui, Pan; Zhiqiang, Lin; Jonathan M, Dreyfuss; Fernando D, Camargo; Ji, Miao; +1 Authors

YAP suppresses gluconeogenic gene expression through PGC1α

Abstract

Cell growth and proliferation are tightly coupled to metabolism, and dissecting the signaling molecules which link these processes is an important step toward understanding development, regeneration, and cancer. The transcriptional regulator Yes‐associated protein 1 (YAP) is a key regulator of liver size, development, and function. We now show that YAP can also suppress gluconeogenic gene expression. Yap deletion in primary hepatocytes potentiates the gluconeogenic gene response to glucagon and dexamethasone, whereas constitutively active YAP suppresses it. The effects of YAP are mediated by the transcriptional coactivator peroxisome proliferator–activated receptor‐gamma coactivator 1. YAP inhibits its ability to bind to and activate transcription from the promoters of its gluconeogenic targets, and the effects of YAP are blunted upon its knockdown. In vivo, constitutively active YAP lowers plasma glucose levels and increases liver size. Conclusion: YAP appears to reprogram cellular metabolism, diverting substrates away from the energy‐consuming process of gluconeogenesis and toward the anabolic process of growth. (Hepatology 2017;66:2029–2041)

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Keywords

Male, Carcinoma, Hepatocellular, Liver Neoplasms, Primary Cell Culture, Gluconeogenesis, Cell Cycle Proteins, YAP-Signaling Proteins, Hep G2 Cells, Phosphoproteins, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Mice, Random Allocation, Gene Expression Regulation, Glucose-6-Phosphatase, Animals, Humans, Phosphoenolpyruvate Carboxykinase (GTP), Adaptor Proteins, Signal Transducing, Transcription Factors

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    popularity
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    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
59
Top 10%
Top 10%
Top 10%
bronze
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