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Two-signal requirement for growth-promoting function of Yap in hepatocytes.

ABSTRACT: The transcriptional coactivator Yes-associated protein (Yap) promotes proliferation and inhibits apoptosis, suggesting that Yap functions as an oncogene. Most oncogenes, however, require a combination of at least two signals to promote proliferation. In this study, we present evidence that Yap activation is insufficient to promote growth in the otherwise normal tissue. Using a mosaic mouse model, we demonstrate that Yap overexpression in a fraction of hepatocytes does not lead to their clonal expansion, as proliferation is counterbalanced by increased apoptosis. To shift the activity of Yap towards growth, a second signal provided by tissue damage or inflammation is required. In response to liver injury, Yap drives clonal expansion, suppresses hepatocyte differentiation, and promotes a progenitor phenotype. These results suggest that Yap activation is insufficient to promote growth in the absence of a second signal thus coordinating tissue homeostasis and repair.

SUBMITTER: Su T

PROVIDER: S-EPMC4363878 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Two-signal requirement for growth-promoting function of Yap in hepatocytes.

Su Tian T Bondar Tanya T Zhou Xu X Zhang Cuiling C He Hang H Medzhitov Ruslan R

eLife 20150210

The transcriptional coactivator Yes-associated protein (Yap) promotes proliferation and inhibits apoptosis, suggesting that Yap functions as an oncogene. Most oncogenes, however, require a combination of at least two signals to promote proliferation. In this study, we present evidence that Yap activation is insufficient to promote growth in the otherwise normal tissue. Using a mosaic mouse model, we demonstrate that Yap overexpression in a fraction of hepatocytes does not lead to their clonal ex ...[more]

PMID: 25667983

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Two-signal requirement for growth-promoting function of Yap

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