2015
DOI: 10.1021/jm501615v
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The Hippo Pathway and YAP/TAZ–TEAD Protein–Protein Interaction as Targets for Regenerative Medicine and Cancer Treatment

Abstract: The Hippo pathway is an important organ size control signaling network and the major regulatory mechanism of cell-contact inhibition. Yes associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are its targets and terminal effectors: inhibition of the pathway promotes YAP/TAZ translocation to the nucleus, where they interact with transcriptional enhancer associate domain (TEAD) transcription factors and coactivate the expression of target genes, promoting cell proliferation. Defe… Show more

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Cited by 145 publications
(134 citation statements)
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References 84 publications
(246 reference statements)
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“…Two small molecule inhibitors that block the YAP-TEAD interaction were identified from John Hopkins Drug Library by drug screening (42). Both Verteporfin (VP, trade name Visudyne by Novartis) and protoporphyrin IX (PPIX) inhibit the YAP-TEAD complex formation at 10 μM in Co-immunoprecipitation assays (43). VP is a FDA-approved photosensitizer in the photodynamic therapy of neovascular macular degeneration; however, when used as an inhibitor of the YAP-TEAD interaction, light activation is not required (43,44).…”
Section: Direct Interruption Of Yap-tead Mediated Transcriptional Actmentioning
confidence: 99%
See 1 more Smart Citation
“…Two small molecule inhibitors that block the YAP-TEAD interaction were identified from John Hopkins Drug Library by drug screening (42). Both Verteporfin (VP, trade name Visudyne by Novartis) and protoporphyrin IX (PPIX) inhibit the YAP-TEAD complex formation at 10 μM in Co-immunoprecipitation assays (43). VP is a FDA-approved photosensitizer in the photodynamic therapy of neovascular macular degeneration; however, when used as an inhibitor of the YAP-TEAD interaction, light activation is not required (43,44).…”
Section: Direct Interruption Of Yap-tead Mediated Transcriptional Actmentioning
confidence: 99%
“…Both Verteporfin (VP, trade name Visudyne by Novartis) and protoporphyrin IX (PPIX) inhibit the YAP-TEAD complex formation at 10 μM in Co-immunoprecipitation assays (43). VP is a FDA-approved photosensitizer in the photodynamic therapy of neovascular macular degeneration; however, when used as an inhibitor of the YAP-TEAD interaction, light activation is not required (43,44). VP alters YAP conformation when binding to it, and abolished its interaction to TEAD (45).…”
Section: Direct Interruption Of Yap-tead Mediated Transcriptional Actmentioning
confidence: 99%
“…Transcriptional coactivator with PDZ-binding motif (TAZ; also known by gene name WW domain-containing transcription regulator 1, WWTR1) functions as a key effector in Hippo pathway cascade, which controls the balance between proliferation and apoptosis and regulates organ size through interaction with various transcription factors, particularly TEA domain family members 1. It has been well-documented that TAZ is involved in many cellular progresses, such as induction of proliferation, migration and increased metastatic potential, and inhibition of apoptosis, among others 2,3.…”
Section: Introductionmentioning
confidence: 99%
“…Phosphorylation of S127 of YAP/TAZ is considered an exclusion signal for nuclear accumulation, leading to ubiquitination (1,3,4). Hence, activation of the Hippo pathway leads to inhibition of YAP/TAZ proteins.…”
mentioning
confidence: 99%
“…Upstream regulators of the Hippo pathway are Merlin, which is encoded by NF2. In confluent cells, Merlin/NF2 are preferentially localised in close proximity to adherens and tight junctions, and this location has been associated with the known activation of the Hippo pathway and inhibition of YAP/TAZ in cell-cell contact inhibition (1,3,4). YAP/TAZ is a known sensor for mechanical stimuli including matrix stiffness, stretch and cell density.…”
mentioning
confidence: 99%