TEAD mediates YAP-dependent gene induction and growth control.

By Bin Zhao, X. Ye, Jindan Yu, Li Li, Weiquan Li, Siming Li, Jianjun Yu, Jiandie D. Lin, Cun-Yu Wang, Arul M. Chinnaiyan and 2 more. Genes & Development, 2008

2,412 citations recorded by the source corpus.

The YAP transcription coactivator has been implicated as an oncogene and is amplified in human cancers. Recent studies have established that YAP is phosphorylated and inhibited by the Hippo tumor suppressor pathway. Here we demonstrate that the TEAD family transcription factors are essential in mediating YAP-dependent gene expression. TEAD is also required for YAP-induced cell growth, oncogenic transformation, and epithelial-mesenchymal transition. CTGF is identified as a direct YAP target gene important for cell growth. Moreover, the functional relationship between YAP and TEAD is conserved in Drosophila Yki (the YAP homolog) and Scalloped (the TEAD homolog). Our study reveals TEAD as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/01caba4e4a5b7487113a843b5bd8213305c977e1

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. S. Piccolo
3. G. Halder
4. Fa-Xing Yu
5. Bin Zhao
6. Randy L. Johnson
7. M. Cordenonsi
8. H. Park

In Molecular Biology

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

Citations in the corpus

• Regulation of the Hippo-YAP pathway by G-protein coupled receptor signaling (2012, background): “YAPactsmainly through TEAD family transcription factors to stimulate expression of genes that promote proliferation and inhibit apoptosis (Zhao et al., 2008).”
• Blastocyst lineage formation, early embryonic asymmetries and axis patterning in the mouse (2009, background): “In Drosophila and mammalian cells, TEAD factors can only activate transcription in combination with a co-activator, Yorkie (Yki) in Drosophila or Yap (Yes-associated protein) in mammals (Vassilev et al., 2001; Zhao et al., 2008).”
• A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF(beta-TRCP). (2010, background): “Nevertheless, there is evidence that at least some of these sites are important for YAP regulation because the YAP-5SA mutant, in which serine residues in all five HXRXXS motifs are mutated to alanines, is more active than YAP-S127A in promoting cell proliferation (Zhao et al. 2009).”
• Angiomotin is a novel Hippo pathway component that inhibits YAP oncoprotein. (2011, background): “YAP promotes cell proliferation and inhibits apoptosis by activating target transcription factors, such as the TEAD family transcription factors (Zhao et al. 2008), to induce gene expression.”
• The Hippo signaling pathway in stem cell biology and cancer (2014, positive): “Conversely, dephosphorylated YAP acts mainly through TEAD family transcription factors to promote cell proliferation and organ growth [24].”
• YAP/TAZ at the roots of cancer (2016, background): “…(Bhat et al., 2011; Chan et al., 2009; Galli et al., 2015; Kapoor et al., 2014; Stein et al., 2015; Xia et al., 2014; Zanconato et al., 2015; Zhao et al., 2008), to the extent that inhibiting YAP/TAZ-TEAD interaction represents one of the most promising avenues for antiYAP/TAZ therapeutic…”
• The Hippo pathway target, YAP, promotes metastasis through its TEAD-interaction domain (2012, background): “Several groups have used mutant forms of YAP containing the S94A mutation or the corresponding murine S79A mutation to demonstrate the importance of the TEAD family of transcription factors in YAP-mediated processes (10, 11, 40, 59).”
• Genetic and pharmacological disruption of the TEAD-YAP complex suppresses the oncogenic activity of YAP. (2012, background): “To screen for such inhibitors, we took advantage of an established luciferase reporter assay in which transcriptional activity of a Gal4-TEAD4 fusion is stimulated by YAP (Zhao et al. 2008).”
• The Hippo Signaling Pathway in Development and Cancer (2010, background): “Consistent with these findings, overexpression of YAP or TAZ can induce anchorage-independent growth and EMT of immortalized mammary and pancreatic epithelial cells in vitro (Overholtzer et al., 2006; Zhao et al., 2008; Zhang et al., 2009a; Chan et al., 2009; Dong et al., 2007).”
• The Hippo signalling pathway and its implications in human health and diseases (2022, background): “21,148 The Hippo pathway has been shown to restrict the proliferation of cardiomyocytes, 10,149 the molecular mechanism in which involves the Wnt 150 or Pi3kcb-mediated PI3K-AKT 151 signalling pathways.”
• The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease (2014, background): “…that disrupt the binding of TAZ or YAP to TEADs abolish their ability to promote proliferation and tumorigenic overgrowth phenotypes (Lamar et al., 2012; Zhang et al., 2009; Zhao et al., 2008), suggesting that control of TEAD activity is crucial for many of the TAZ/YAP functions described.”
• Hippo Pathway in Organ Size Control, Tissue Homeostasis, and Cancer. (2015, positive): “In addition, YAP/TAZ induce expression of angiomotin-like protein 2 (AMOTL2), a negative regulator of YAP (Mohseni et al., 2014; Zhao et al., 2008).”