hippo encodes a Ste-20 family protein kinase that restricts cell proliferation and promotes apoptosis in conjunction with salvador and warts.

By Shian Wu, Jianbin Huang, Jixin Dong, Duojia Pan. Cell, 2003

1,158 citations recorded by the source corpus.

The coordination between cell proliferation and cell death is essential to maintain homeostasis within multicellular organisms. The mechanisms underlying this regulation are yet to be completely understood. Here, we report the identification of hippo (hpo) as a gene that regulates both cell proliferation and cell death in Drosophila. hpo encodes a Ste-20 family protein kinase that binds to and phosphorylates the tumor suppressor protein Salvador (Sav), which is known to interact with the Warts (Wts) protein kinase. Loss of hpo results in elevated transcription of the cell cycle regulator cyclin E and the cell-death inhibitor diap1, leading to increased proliferation and reduced apoptosis. Further, we show that hpo, sav, and wts define a pathway that regulates diap1 at the transcriptional level. A human homolog of hpo completely rescues the overgrowth phenotype of Drosophila hpo mutants, suggesting that hpo might play a conserved role for growth control in mammals.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/64b0054d87184ad83a46cd224b69d6adf5674f7e

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In Cell Biology

1. K. Guan
2. Bin Zhao
3. G. Halder
4. Duojia Pan
5. Fa-Xing Yu
6. S. Piccolo
7. Randy L. Johnson
8. M. Cordenonsi

In Molecular Biology

1. K. Guan
2. Bin Zhao
3. Duojia Pan
4. G. Halder
5. Randy L. Johnson
6. Fa-Xing Yu
7. S. Piccolo
8. Xaralabos Varelas

Citations in the corpus

• Mst1 and Mst2 maintain hepatocyte quiescence and suppress the development of hepatocellular carcinoma through inactivation of the Yap1 oncogene (2009, positive): “Loss of both Mst1 and Mst2 is sufficient to initiate hepatocyte proliferation, resulting in dramatic liver overgrowth, resistance to pro-apoptotic *Address correspondence to: Nabeel Bardeesy Ph.D., Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School,…”
• Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control. (2007, background): “Hippo (Hpo) is a Ste20 family protein kinase that complexes with a regulatory scaffold protein Salvador (Sav) (Kango-Singh et al. 2002; Tapon et al. 2002; Harvey et al. 2003; Pantalacci et al. 2003; Udan et al. 2003; Wu et al. 2003).”
• The Hippo Signaling Pathway in Development and Cancer (2010, background): “Biochemically, these four tumor suppressors form a kinase cascade in which the Hpo-Sav kinase complex phosphorylates and activates the Wts-Mats kinase complex (Wu et al., 2003; Wei et al., 2007).”
• Hippo signaling: growth control and beyond (2011, background): “Roles of Scalloped and Yorkie in Drosophila In Drosophila imaginal discs, the TEAD family transcription factor Scalloped (Sd) primarily mediates the function of Yki, which itself does not bind to DNA (Goulev et al., 2008; Wu et al., 2008; Zhang et al., 2008b; Zhao et al., 2008a).”
• The Hippo pathway: regulators and regulations. (2013, background): “…Mob all lead to significant tissue outgrowth, as indicated by enlarged eyes, wings, or other appendages (Justice et al. 1995; Xu et al. 1995; Kango-Singh et al. 2002; Tapon et al. 2002; Harvey et al. 2003; Jia et al. 2003; Pantalacci et al. 2003; Udan et al. 2003; Wu et al. 2003; Lai et al. 2005).”
• The TEAD/TEF family protein Scalloped mediates transcriptional output of the Hippo growth-regulatory pathway. (2008, methodology): “Among the beststudied Hpo pathway targets—cycE, diap1, and the microRNA bantam—we focused on diap1 since its regulation by the Hpo pathway is more robust and ubiquitous in the eye imaginal discs than that of cycE (Wu et al., 2003; Huang et al., 2005), and microRNA promoters are less well defined tha”
• Control of cell proliferation and apoptosis by mob as tumor suppressor, mats. (2005, background): “Cell overproliferation and apoptosis phenotypes caused by mats mutations are strikingly similar to those induced by loss-of-function mutations in hpo, sav, and wts genes, suggesting that mats may function in the Hpo-Sav-Wts pathway.”
• The Hippo-YAP pathway in organ size control and tumorigenesis: an updated version. (2010, background): “Other important questions include the biochemical mechanism of Mst1/2/Sav1 activation by upstream components.”
• Hippo signaling in organ size control. (2007, methodology): “…imaginal discs were the introduction of the yeast FRT/FLP recombination system (Golic and Lindquist 1989) and the development of FRT/FLPbased techniques for generating mosaics, which allow one to analyze homozygous mutant clones in an otherwise heterozygous background (Xu and Rubin 1993).”
• The Hippo signaling pathway coordinately regulates cell proliferation and apoptosis by inactivating Yorkie, the Drosophila Homolog of YAP. (2005, background): “…et al., 2004). hpo, sav, and wts (also called lats) were identified from genetic screens in Drosophila for negative regulators of tissue growth (Xu et al., 1995; Justice et al., 1995; Tapon et al., 2002; Kango-Singh et al., 2002; Harvey et al., 2003; Wu et al., 2003; Jia et al., 2003; Udan et…”
• CDK8/9 drive Smad transcriptional action, turnover and YAP interactions in BMP and TGFβ pathways (2009, neutral): “of mammalian and Drosophila S2 cells and siRNA oligonucleotides were as described (Sapkota et al., 2007; Wu et al., 2003; Knockaert et al., 2006).”