Transcriptional Co-repressor Function of the Hippo Pathway Transducers YAP and TAZ

Kim, Min‐Chul; Kim, Taekhoon; Johnson, Randy L.; Lim, Dae–Sik

doi:10.1016/j.celrep.2015.03.015

Cited by 249 publications

(259 citation statements)

References 43 publications

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“…Many studies to data have focused on identifying genes upregulated by YAP/TAZ [22]. Here, we unequivocally demonstrate that YAP is a repressor of S100A7 induction via the Hippo pathway in A431 cells.…”

Section: Introductionsupporting

confidence: 50%

S100A7 induction is repressed by YAP via the Hippo pathway in A431 cells

Kong

Wang

et al. 2016

Oncotarget

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YAP is an oncogenic transcriptional co-activator and is inhibited by the Hippo pathway. Recent studies have revealed that YAP is also a sensor of cell morphology and cell density and can be phosphorylated by cytoskeleton reorganization. Our previous study demonstrated that S100A7 was upregulated in several squamous cell carcinoma (SCC) specimens and was dramatically induced in SCC cells by suspension and dense culture as well as in xenografts. However, little is known about how S100A7 induction occurs in cancer cells. Here, we identify that S100A7 induction is accompanied by YAP phosphorylation in both suspended and dense A431 cells. This correlation reverses after recovery of cell attachment or relief from dense culture. Further examination finds that S100A7 induction is repressed by nuclear YAP, which is further validated by activation or inhibition of the Hippo pathway via loss- and/or gain-of- LATS1 and MST1 function. Strikingly, disruption of the F-actin promotes S100A7 expression via YAP by activation of the Hippo pathway. Furthermore, we demonstrate that repression of S100A7 by YAP required TEAD1 transcriptional factor. Taken together, our findings demonstrate for the first time that S100A7 is repressed by YAP via the Hippo pathway.

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Section: Introductionsupporting

confidence: 50%

S100A7 induction is repressed by YAP via the Hippo pathway in A431 cells

Kong

Wang

et al. 2016

Oncotarget

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“…Recent studies demonstrated that YAP can function as a transcription repressor through recruitment of the NuRD complex in certain genomic regions (Beyer et al, 2013; Kim et al, 2015). It prompted us to examine whether YAP may directly repress Myocd transcription in the context of smooth muscle cell differentiation.…”

Section: Resultsmentioning

confidence: 99%

YAP/TAZ and Hedgehog Coordinate Growth and Patterning in Gastrointestinal Mesenchyme

Cotton

et al. 2017

Developmental Cell

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SUMMARY YAP/TAZ are the major mediators of mammalian Hippo signaling; however, their precise function in the gastrointestinal tract remains poorly understood. Here we dissect the distinct roles of YAP/TAZ in endodermal epithelium and mesenchyme, and find that, although dispensable for gastrointestinal epithelial development and homeostasis, YAP/TAZ function as the critical molecular switch to coordinate growth and patterning in gut mesenchyme. Our genetic analyses reveal that Lats1/2 kinases suppress expansion of the primitive mesenchymal progenitors, where YAP activation also prevents induction of the smooth muscle lineage through transcriptional repression of Myocardin. During later development, zone-restricted down-regulation of YAP/TAZ provides the positional cue and allows smooth muscle cell differentiation induced by Hedgehog signaling. Taken together, our studies identify the mesenchymal requirement of YAP/TAZ in the gastrointestinal tract, and highlight the functional interplays between Hippo and Hedgehog signaling underlying temporal and spatial control of tissue growth and specification in developing gut.

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“…It will be interesting to learn whether the same mechanism holds true for other YAP/TAZ-utilized TFs. In some instances YAP/TAZ also operate as transcriptional corepressors for additional target genes [43,79,80]. Intriguingly this nuclear function also requires TEAD TFs [43,80].…”

Section: Nuclear Functions Of Yap and Tazmentioning

confidence: 99%

YAP and TAZ: a nexus for Hippo signaling and beyond

Hansen

Moroishi

Guan

2015

Trends in Cell Biology

473

482

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The Hippo pathway is a potent regulator of cellular proliferation, differentiation, and tissue homeostasis. Here we review the regulatory mechanisms of the Hippo pathway and discuss the function of Yes-associated protein (YAP)/transcriptional coactivator with a PDZ-binding domain (TAZ), the prime mediators of the Hippo pathway, in stem cell biology and tissue regeneration. We highlight their activities in both the nucleus and the cytoplasm and discuss their role as a signaling nexus and integrator of several other prominent signaling pathways such as the Wnt, G protein-coupled receptor (GPCR), epidermal growth factor (EGF), BMP/transforming growth factor beta (TGFβ), and Notch pathways.

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Transcriptional Co-repressor Function of the Hippo Pathway Transducers YAP and TAZ

Cited by 249 publications

References 43 publications

S100A7 induction is repressed by YAP via the Hippo pathway in A431 cells

S100A7 induction is repressed by YAP via the Hippo pathway in A431 cells

YAP/TAZ and Hedgehog Coordinate Growth and Patterning in Gastrointestinal Mesenchyme

YAP and TAZ: a nexus for Hippo signaling and beyond

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