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 F. Gayyed, Robert A. Anders, Anirban Maitra, Duojia Pan

Research output: Contribution to journalArticle

1257 Citations (Scopus)

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

Fingerprint

Phosphorylation
Mammals
Drosophila
Organ Size
Tissue homeostasis
Cell proliferation
Cell death
Growth
Transgenic Mice
Carcinogenesis
Homeostasis
Cell Death
Phosphotransferases
Cell Proliferation

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., ... Pan, 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

Elucidation of a Universal Size-Control Mechanism in Drosophila and Mammals. / Dong, Jixin; Feldmann, Georg; Huang, Jianbin; Wu, Shian; Zhang, Nailing; Comerford, Sarah A.; Gayyed, Mariana F F.; Anders, Robert A.; Maitra, Anirban; Pan, Duojia.

In: Cell, Vol. 130, No. 6, 21.09.2007, p. 1120-1133.

Research output: Contribution to journalArticle

Dong, J, Feldmann, G, Huang, J, Wu, S, Zhang, N, Comerford, SA, Gayyed, MFF, Anders, RA, Maitra, A & Pan, D 2007, 'Elucidation of a Universal Size-Control Mechanism in Drosophila and Mammals', Cell, vol. 130, no. 6, pp. 1120-1133. https://doi.org/10.1016/j.cell.2007.07.019
Dong J, Feldmann G, Huang J, Wu S, Zhang N, Comerford SA et al. Elucidation of a Universal Size-Control Mechanism in Drosophila and Mammals. Cell. 2007 Sep 21;130(6):1120-1133. https://doi.org/10.1016/j.cell.2007.07.019
Dong, Jixin ; Feldmann, Georg ; Huang, Jianbin ; Wu, Shian ; Zhang, Nailing ; Comerford, Sarah A. ; Gayyed, Mariana F F. ; Anders, Robert A. ; Maitra, Anirban ; Pan, Duojia. / Elucidation of a Universal Size-Control Mechanism in Drosophila and Mammals. In: Cell. 2007 ; Vol. 130, No. 6. pp. 1120-1133.
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