Hippo signaling in organ size control.

By Duojia Pan. Genes & Development, 2007

686 citations recorded by the source corpus.

The control of organ (or organism) size is a fundamental aspect of life that has long captured human imagination. What makes an elephant grow a million times larger than a mouse? How do our two hands develop independently of each other yet reach very similar size? How does a liver precisely regenerate its original mass when two-thirds of it is removed? The recent discovery of a novel signaling network in Drosophila, known as the Hippo (Hpo) pathway, might provide an important entry point to these fascinating questions. The Hpo pathway consists of several negative growth regulators acting in a kinase cascade that ultimately phosphorylates and inactivates Yorkie (Yki), a transcriptional coactivator that positively regulates cell growth, survival, and proliferation. Components of the Hpo pathway are highly conserved throughout evolution, suggesting that this pathway may function as a global regulator of tissue homeostasis in all metazoan animals. Here, I provide a historical review of this potent growth-regulatory pathway and highlight outstanding questions that will likely be the focus of future investigation.

Subfields: Cell Biology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/88a1641170c35bfd3f174e2fa0cd3fb44ace09a2

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. K. Guan
2. G. Halder
3. Bin Zhao
4. Duojia Pan
5. Fa-Xing Yu
6. Yonggang Zheng
7. Randy L. Johnson
8. Li Li

In Molecular Biology

1. K. Guan
2. Duojia Pan
3. Bin Zhao
4. G. Halder
5. Fa-Xing Yu
6. Yonggang Zheng
7. Li Li
8. K. Tumaneng

In Oncology

1. L. Jan
2. Y. Jan
3. K. Guan
4. Bin Zhao
5. Duojia Pan
6. J. Massagué
7. Y. Xiong
8. G. Halder

Citations in the corpus

• Elucidation of a universal size-control mechanism in Drosophila and mammals. (2007, background): “Recent studies in the fruit fly Drosophila have implicated the Hippo signaling pathway as an intrinsic mechanism that restricts organ size in development (Edgar, 2006; Pan, 2007).”
• TAZ Promotes Cell Proliferation and Epithelial-Mesenchymal Transition and Is Inhibited by the Hippo Pathway (2008, background): “YAP is a candidate human oncogene in the amplicon 11q22 (23).”
• The TEAD/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control. (2008, background): “A number of tumor suppressors fall into an emerging tumor suppressor pathway, the so-called Hippo (Hpo) pathway (Edgar, 2006; Pan, 2007).”
• The Hippo Signaling Pathway in Development and Cancer (2010, background): “Thus, from these pioneering studies, a kinase cascade leading from Hpo to Yki phosphorylation emerged (reviewed in Edgar, 2006; Pan, 2007).”
• Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. (2007, background): “Recent genetic studies in Drosophila have shown that the Hippo signaling pathway plays a key role in restricting organ size by controlling both cell proliferation and apoptosis (Edgar 2006; Harvey and Tapon 2007; Pan 2007).”
• Regulation of the Hippo-YAP pathway by G-protein coupled receptor signaling (2012, background): “The Hippo pathway was initially defined by genetic studies in Drosophila, wherein mosaic mutations of Hippo pathway genes resulted in tissue overgrowth (reviewed in Pan, 2007).”
• A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP). (2010, background): “Regulation of YAP/ Yki activity was first revealed by genetic studies of the Hippo tumor suppressor pathway in Drosophila (KangoSingh et al. 2002; Tapon et al. 2002; Harvey et al. 2003; Jia et al. 2003; Pantalacci et al. 2003; Udan et al. 2003; S Wu et al. 2003; Lai et al. 2005).”
• Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment (2013, background): “YAP acts in concert with TEAD transcriptional factors to increase downstream CCN growth factors and baculoviral inhibitors of apoptosis repeat containing (BIRC) apoptosis inhibitors (7).”
• The TEAD/TEF family protein Scalloped mediates transcriptional output of the Hippo growth-regulatory pathway. (2008, background): “Studies in recent years, primarily conducted in the fruit fly Drosophila, have implicated the Hippo (Hpo) signaling pathway as a central mechanism that regulates organ size by controlling both cell proliferation and cell death (Edgar, 2006; Pan, 2007; Harvey and Tapon, 2007).”
• Branching out: mechanisms of dendritic arborization (2010, background): “Hippo , a kinase of the STE20 family, is a major regulator of organ size in flies and mammal”
• The Hippo signaling pathway components Lats and Yap pattern Tead4 activity to distinguish mouse trophectoderm from inner cell mass. (2009, background): “In mammals, Hippo signaling comprises a growth-regulating pathway, which controls cell contact-mediated inhibition of proliferation (see reviews Pan, 2007; Reddy and Irvine, 2008; Saucedo and Edgar, 2007).”
• Hippo pathway regulation by cell morphology and stress fibers (2011, background): “INTRODUCTION The Hippo signaling pathway is an evolutionarily conserved tumorsuppressor signaling pathway that plays an important role in regulation of cell proliferation (see Halder and Johnson, 2011; Pan, 2007; Reddy and Irvine, 2008; Saucedo and Edgar, 2007).”
• CDK8/9 drive Smad transcriptional action, turnover and YAP interactions in BMP and TGFβ pathways (2009, positive): “The top-scoring hit was YAP (Figure 6A), a transcriptional coactivator that binds PY motifs of target proteins (Edgar, 2006; Pan, 2007; Zeng and Hong, 2008).”