Elucidation of a Universal Size-Control Mechanism in Drosophila and Mammals

Jixin Dong, Georg Feldmann, Jianbin Huang, Shian Wu, Nailing Zhang, Sarah A Comerford, Mariana F Gayyed, Robert A. Anders, Anirban Maitra, Duojia Pan Ph.D.

Research output: Contribution to journalArticle

1328 Scopus citations

Abstract

Coordination of cell proliferation and cell death is essential to attain proper organ size during development and for maintaining tissue homeostasis throughout postnatal life. In Drosophila, these two processes are orchestrated by the Hippo kinase cascade, a growth-suppressive pathway that ultimately antagonizes the transcriptional coactivator Yorkie (Yki). Here we demonstrate that a single phosphorylation site in Yki mediates the growth-suppressive output of the Hippo pathway. Hippo-mediated phosphorylation inactivates Yki by excluding it from the nucleus, whereas loss of Hippo signaling leads to nuclear accumulation and therefore increased Yki activity. We further delineate a mammalian Hippo signaling pathway that culminates in the phosphorylation of YAP, the mammalian homolog of Yki. Using a conditional YAP transgenic mouse model, we demonstrate that the mammalian Hippo pathway is a potent regulator of organ size, and that its dysregulation leads to tumorigenesis. These results uncover a universal size-control mechanism in metazoan.

Original languageEnglish (US)
Pages (from-to)1120-1133
Number of pages14
JournalCell
Volume130
Issue number6
DOIs
StatePublished - Sep 21 2007

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Keywords

  • DEVBIO
  • SIGNALING

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Dong, J., Feldmann, G., Huang, J., Wu, S., Zhang, N., Comerford, S. A., Gayyed, MF., Anders, R. A., Maitra, A., & Pan Ph.D., D. (2007). Elucidation of a Universal Size-Control Mechanism in Drosophila and Mammals. Cell, 130(6), 1120-1133. https://doi.org/10.1016/j.cell.2007.07.019