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

Su T, Bondar T, Zhou X, Zhang C, He H, Medzhitov R - Elife (2015)

Bottom Line: The transcriptional coactivator Yes-associated protein (Yap) promotes proliferation and inhibits apoptosis, suggesting that Yap functions as an oncogene.To shift the activity of Yap towards growth, a second signal provided by tissue damage or inflammation is required.These results suggest that Yap activation is insufficient to promote growth in the absence of a second signal thus coordinating tissue homeostasis and repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.

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.

No MeSH data available.


Related in: MedlinePlus

Hematopoietic cell numbers undergo similar changes in response to CCl4 in the WT and YapKIAlb-Cre mice.CD45+ cell numbers were measured by quantitative flow cytometry in the supernatant fractions of cells isolated from collagenase-perfused livers at indicated times after CCl4 treatment.DOI:http://dx.doi.org/10.7554/eLife.02948.018
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fig3s5: Hematopoietic cell numbers undergo similar changes in response to CCl4 in the WT and YapKIAlb-Cre mice.CD45+ cell numbers were measured by quantitative flow cytometry in the supernatant fractions of cells isolated from collagenase-perfused livers at indicated times after CCl4 treatment.DOI:http://dx.doi.org/10.7554/eLife.02948.018


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

Su T, Bondar T, Zhou X, Zhang C, He H, Medzhitov R - Elife (2015)

Hematopoietic cell numbers undergo similar changes in response to CCl4 in the WT and YapKIAlb-Cre mice.CD45+ cell numbers were measured by quantitative flow cytometry in the supernatant fractions of cells isolated from collagenase-perfused livers at indicated times after CCl4 treatment.DOI:http://dx.doi.org/10.7554/eLife.02948.018
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4363878&req=5

fig3s5: Hematopoietic cell numbers undergo similar changes in response to CCl4 in the WT and YapKIAlb-Cre mice.CD45+ cell numbers were measured by quantitative flow cytometry in the supernatant fractions of cells isolated from collagenase-perfused livers at indicated times after CCl4 treatment.DOI:http://dx.doi.org/10.7554/eLife.02948.018
Bottom Line: The transcriptional coactivator Yes-associated protein (Yap) promotes proliferation and inhibits apoptosis, suggesting that Yap functions as an oncogene.To shift the activity of Yap towards growth, a second signal provided by tissue damage or inflammation is required.These results suggest that Yap activation is insufficient to promote growth in the absence of a second signal thus coordinating tissue homeostasis and repair.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, United States.

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.

No MeSH data available.


Related in: MedlinePlus