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Cited by 2,370Hippo pathway signaling and YAP/TAZMicrotubule and mitosis dynamicsPI3K/AKT/mTOR signaling in cancer

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

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Dong, Jixin, Feldmann, Georg, Huang, Jianbin, Wu, Shian, Zhang, Nailing, Comerford, Sarah A., Gayyed, Mariana F., Anders, Robert A., Maitra, Anirban, Pan, Duojia·2007·Cell
DOI 10.1016/j.cell.2007.07.019PMC PMC2666353
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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.

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Metadata

Authors
Dong, J., Feldmann, G., Huang, J., Wu, S., Zhang, N., Comerford, S. A., Gayyed, M. F., Anders, R. A., Maitra, A., & Pan, D.
Affiliations
  • Johns Hopkins University (US)
  • The University of Texas Southwestern Medical Center (US)
Corresponding author
Pan, Duojia
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2007-09
Volume
130
Issue
6
Pages
1120-1133
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2007.07.019
PMC
PMC2666353
OpenAlex
W2141595533
Cited by
2,370
References
4
Citations by year
2026: 70 · 2025: 102 · 2024: 125 · 2023: 122 · 2022: 187 · 2021: 161 · 2020: 159 · 2019: 167 · 2018: 175 · 2017: 143 · 2016: 146 · 2015: 171 · 2014: 134 · 2013: 121 · 2012: 97
FWCI
27.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Eye Institute (EY015708, R01EY015708)
  • National Cancer Institute (R01CA113669)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK081417, R21DK072532, DK067187, K08DK067187)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
Hippo signaling pathway, Yorkie, YAP, organ size control, cell proliferation, cell death, nuclear localization, phosphorylation, growth inhibition, tissue homeostasis, carcinogenesis, Drosophila
MeSH terms
Serine-Threonine Kinase 3, YAP-Signaling Proteins, Hippo Kinases, Animals, Cell Line, Cell Nucleus, Cytoplasm, Doxorubicin, Drosophila, Homeostasis, Humans, Liver Neoplasms, Experimental, Mammals, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Nuclear Proteins, Organ Size, Phosphorylation, Protein Kinases, Serine, Transcription Factors, Transfection, Signal Transduction, Trans-Activators, Apoptosis, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Active Transport, Cell Nucleus, Large Neutral Amino Acid-Transporter 1, Drosophila Proteins, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Signal Transducing, Cell Proliferation, Mice

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