Affinage

WWTR1

WW domain-containing transcription regulator protein 1 · UniProt Q9GZV5

Length
400 aa
Mass
44.1 kDa
Annotated
2026-06-11
63 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

WWTR1 (TAZ) is a transcriptional coactivator that converts mechanical and developmental signals into TEAD-dependent gene programs governing organ size, cell fate, and tissue mechanosensing (PMID:36037374, PMID:28068223). It functions by binding transcription factors through a WW/P-LPXY motif interface — demonstrated for Glis3, where TAZ enhances Glis3-driven transcription and motif mutations abolish both binding and activity (PMID:19273592) — and acts as a modifier of NKX2-1 transactivation (PMID:29294041). TAZ activity is gated by its subcellular localization: GSK3 phosphorylates an N-terminal phosphodegron that recruits the SCF(β-TrCP) E3 ligase for ubiquitylation and proteasomal degradation when PI3K signaling is low, so that PTEN loss stabilizes TAZ (PMID:22692215), while 14-3-3 binding and competition with AMOT/F-actin retain TAZ in the cytoplasm; relief of these constraints drives nuclear translocation and target-gene activation (PMID:35411948, PMID:35822241). In tissues, nuclear TAZ controls renal cilia integrity (PMID:17251353), compact-wall and trabecular cardiac architecture via Fibronectin assembly and Nrg/Erbb2-regulated nuclear export (PMID:29283341, PMID:29773645), trophoblast self-renewal and differentiation through WNT components (PMID:36037374), osteoblast mechanosensing in concert with Polycystin-1 and through transcriptional control of TβRII (PMID:37884491, PMID:38562782), and corneal endothelial homeostasis (PMID:37074694). TAZ drives fibrosis by activating TEAD-dependent transcription of secreted Indian hedgehog in hepatocytes and of Ccn3 in cardiac myofibroblasts (PMID:28068223, PMID:36998974). Constitutive nuclear activation is oncogenic: the WWTR1-CAMTA1 and WWTR1::TFE3 fusions and the 14-3-3-disrupting S89W mutation all produce TEAD-dependent transformation and tumor formation (PMID:33766984, PMID:33766982, PMID:38380774, PMID:35411948).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 2007 High

    Established that WWTR1 has an essential tissue-level function, linking it to renal ciliary biology before its transcriptional mechanism was resolved.

    Evidence Knockout mouse with glomerulocystic kidney phenotype plus siRNA in mIMCD3 cells downregulating cilia genes

    PMID:17251353

    Open questions at the time
    • Did not identify the transcription factors or direct target genes mediating cilia control
    • Mechanism connecting TAZ to specific cilia genes (Pkhd1, Ofd1) left undefined
  2. 2009 High

    Defined the molecular basis of TAZ coactivation by showing it docks onto a partner transcription factor via a P/LPXY motif to enhance transcription.

    Evidence Co-IP, reporter assays, and P/LPXY motif mutagenesis with Glis3

    PMID:19273592

    Open questions at the time
    • Limited to Glis3; generality of the motif interface to other partners not tested here
    • No structural detail of the WW-domain interaction
  3. 2012 High

    Resolved a degradation arm of TAZ regulation, showing protein abundance is controlled by a GSK3 phosphodegron feeding SCF(β-TrCP), linking TAZ stability to PI3K/PTEN status.

    Evidence In vitro kinase, co-IP, ubiquitylation and phosphodegron mutagenesis in PTEN-mutant cells

    PMID:22692215

    Open questions at the time
    • Relationship between this degron and LATS/14-3-3 cytoplasmic retention not integrated
    • Quantitative contribution to TAZ levels in normal tissue unknown
  4. 2015 High

    Identified constitutive nuclear localization as the core oncogenic mechanism of the WWTR1-CAMTA1 fusion, escaping normal cytoplasmic restraint.

    Evidence Subcellular fractionation, soft-agar transformation, anoikis-resistance assays and transcriptional profiling

    PMID:25961935

    Open questions at the time
    • TEAD-dependency not yet formally tested in this study
    • Cell-of-origin for tumor formation not established here
  5. 2017 High

    Connected TAZ to extracellular matrix morphogenesis, showing it controls Fibronectin assembly during body extension and fin-fold formation.

    Evidence Zebrafish loss-of-function with live imaging and Fibronectin immunofluorescence

    PMID:29283341

    Open questions at the time
    • Transcriptional targets driving Fibronectin assembly not identified
    • Whether effect is cell-autonomous left open
  6. 2018 High

    Established TAZ's role in cardiac compact-wall architecture and revealed Nrg/Erbb2 signaling as an upstream regulator of TAZ nuclear export.

    Evidence Zebrafish mosaic analysis, junction/actin imaging, and Nrg/Erbb2 manipulation with TAZ localization

    PMID:29773645

    Open questions at the time
    • Molecular link between Erbb2 signaling and TAZ export machinery undefined
    • Direct target genes in cardiomyocytes not identified
  7. 2018 Medium

    Showed TAZ modifies NKX2-1 transactivation in lung, extending its coactivator role to a tissue-specific transcription factor and a human syndrome.

    Evidence Co-IP, luciferase reporter assays and mutagenesis of NKX2-1 domains

    PMID:29294041

    Open questions at the time
    • Reporter-based; in vivo relevance to brain-lung-thyroid syndrome not directly tested
    • Binding equal for both mutants leaves functional discrimination mechanism unclear
  8. 2019 High

    Demonstrated TAZ can act as a transcriptional repressor in early embryos, repressing Sox2 with TEAD4/YAP1 to restrain premature pluripotency.

    Evidence Mouse embryo knockouts, Sox2 repression reporter assays and LATS inhibition

    PMID:31444221

    Open questions at the time
    • Mechanism converting TAZ-TEAD from activator to repressor not defined
    • Stage-specific LATS insensitivity unexplained
  9. 2016 High

    Defined a paracrine fibrotic axis in which hepatocyte TAZ drives TEAD-dependent Indian hedgehog secretion to activate stellate-cell fibrogenesis.

    Evidence Hepatocyte-specific gain/loss-of-function in mouse NASH with TEAD-Ihh reporter assays

    PMID:28068223

    Open questions at the time
    • Upstream signal activating hepatocyte TAZ in NASH not identified
    • Effect on steatosis absent, leaving lipid arm separate
  10. 2021 High

    Proved that constitutive TAZ activation is sufficient to cause EHE in vivo and that transformation strictly requires the TAZ-TEAD interaction.

    Evidence Endothelial conditional and knock-in mouse models with dominant-negative TEAD and TEAD-binding-domain disruption

    PMID:33766982 PMID:33766984

    Open questions at the time
    • Specific TEAD target genes driving endothelial transformation not enumerated
    • Why endothelium is the susceptible lineage unresolved
  11. 2021 Medium

    Placed wwtr1 as a direct transcriptional target of Foxc1a in cardiac chamber maturation, identifying an upstream activator of TAZ expression.

    Evidence ChIP, dual-luciferase and wwtr1 mRNA rescue in foxc1a-null zebrafish

    PMID:34923164

    Open questions at the time
    • Conservation of Foxc1a-wwtr1 regulation in mammals untested
    • Whether transcriptional vs post-translational control dominates in this context unclear
  12. 2022 Medium

    Linked TAZ nuclear shuttling to cytoskeletal/AMOT competition and a new autophagy output downstream of SORBS3.

    Evidence SORBS3 knockdown, F-actin manipulation, fractionation and autophagosome quantification

    PMID:35822241

    Open questions at the time
    • Competition inferred without direct binding reconstitution
    • Direct TAZ targets driving autophagosome formation not validated
  13. 2022 Medium

    Showed ZO-2/Tjp2 negatively regulates TAZ protein levels and that TAZ is required for hepatocyte-to-cholangiocyte transdifferentiation.

    Evidence Liver Tjp2 conditional KO, DDC challenge, Western blot and cell-type-specific epistasis

    PMID:36151109

    Open questions at the time
    • Mechanism by which Tjp2 controls TAZ protein abundance not defined
    • Direct target genes of transdifferentiation not identified
  14. 2022 Medium

    Established TAZ as the dominant effector of matrix-stiffness and LPA-induced mesothelial-mesenchymal transition, acting independently of TGF-β1.

    Evidence siRNA knockdown, defined-stiffness hydrogels, TAZ localization imaging and TGF-β1 inhibition

    PMID:35445400

    Open questions at the time
    • Mechanotransduction machinery upstream of TAZ in mesothelium undefined
    • Target genes driving MMT not mapped
  15. 2022 High

    Identified an activating point mutation (S89W) that disrupts 14-3-3 binding to drive constitutive nuclear TAZ and oncogenic phenotypes, mechanistically mirroring the fusion oncoproteins.

    Evidence 14-3-3 binding assay, fractionation, in vitro transformation assays, xenograft and verteporfin reversal

    PMID:35411948

    Open questions at the time
    • Tumor types where S89W occurs not delineated here
    • Whether residual LATS regulation persists not tested
  16. 2022 High

    Defined TAZ as a fate-determining regulator in human trophoblast, promoting self-renewal and EVT differentiation while blocking syncytiotrophoblast fate via WNT components.

    Evidence shRNA/overexpression in trophoblast stem cells and explants with scRNA-seq

    PMID:36037374

    Open questions at the time
    • Direct WNT-component targets bound by TAZ not enumerated
    • Whether action is TEAD-dependent in trophoblast untested
  17. 2023 High

    Demonstrated cooperative mechanosensing between TAZ and Polycystin-1 in osteoblasts, with both required for anabolic loading responses.

    Evidence Osteoblast double conditional KO, micro-CT, mechanical loading and mechanomimetic MS2

    PMID:37884491

    Open questions at the time
    • Molecular link between PC1 and TAZ activation not defined
    • Shared transcriptional targets not identified
  18. 2023 High

    Identified Ccn3 as a TAZ-driven mediator of adverse cardiac fibrotic remodeling, defining a myofibroblast effector downstream of YAP/TAZ.

    Evidence Myofibroblast double conditional KO, MI model, scRNA-seq and recombinant CCN3 administration

    PMID:36998974

    Open questions at the time
    • Direct binding of TAZ to the Ccn3 locus not shown
    • Whether YAP and TAZ are interchangeable here not fully resolved
  19. 2023 Medium

    Established TAZ as essential for corneal endothelial homeostasis and modeled Fuchs' dystrophy, with elevated nuclear TAZ seen in patient tissue.

    Evidence Wwtr1 KO mouse, atomic force microscopy, wound-healing assay and human CEnC analysis

    PMID:37074694

    Open questions at the time
    • Causal link between TAZ loss and guttae formation not mechanistically resolved
    • Transcriptional targets in endothelium not mapped
  20. 2023 Medium

    Showed Wnt16 signals through TAZ to upregulate the vascular smooth muscle contractile program via TAZ binding at the Acta2 promoter and TEAD cognate sites.

    Evidence siRNA, ChIP, promoter reporter, verteporfin and mouse genetic model

    PMID:38123514

    Open questions at the time
    • Link between Wnt16 receptor signaling and TAZ activation undefined
    • YAP non-redundancy mechanism unclear
  21. 2023 Medium

    Showed nuclear TAZ relocalization sensitizes p53-proficient colorectal cancer cells to oxaliplatin, implicating TAZ in chemotherapy response.

    Evidence siRNA/drug loss-of-function, nuclear fractionation and YAP/TAZ inhibitors across p53-defined cell lines

    PMID:38741073

    Open questions at the time
    • TAZ target genes mediating chemosensitivity not identified
    • Mechanistic basis of p53 dependence unresolved
  22. 2024 Medium

    Extended the oncogenic fusion paradigm to WWTR1::TFE3, confirming TEAD-binding is the shared requirement for fusion-driven transformation.

    Evidence Soft-agar transformation in NIH3T3 with TEAD-binding-domain mutagenesis

    PMID:38380774

    Open questions at the time
    • In vivo tumorigenicity not tested
    • Contribution of the TFE3 partner to the program undefined
  23. 2024 Medium

    Defined a transcriptional-plus-stabilization circuit in which TAZ activates TβRII transcription and cooperates with IFT20 to control bone fate.

    Evidence ChIP, ubiquitination/Co-IP and osteoblast double KO in osteoporosis models (preprint)

    PMID:38562782

    Open questions at the time
    • Preprint, awaiting peer review
    • Direct interplay between IFT20-stabilized TβRII and TAZ transcriptional output not fully separated
  24. 2026 Medium

    Linked TAZ-dependent mechanotransduction to organelle stress, showing its loss causes ER stress, mitochondrial defects and dysregulated autophagy/ECM genes in corneal endothelium.

    Evidence scRNA-seq, TEM and immunofluorescence in aged Wwtr1 KO mice (preprint)

    PMID:41756894

    Open questions at the time
    • Preprint, awaiting peer review
    • Direct transcriptional targets connecting TAZ to organelle homeostasis not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TAZ-TEAD complexes are switched between activating and repressive states across tissues, and what defines lineage-specific target-gene selection, remains unresolved.
  • No unified model linking the degron, 14-3-3 and AMOT/cytoskeletal control arms quantitatively
  • Direct genome-wide TAZ targets in most physiological contexts unmapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-1643685 Disease 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4 R-HSA-392499 Metabolism of proteins 1
Partners
AMOTBTRCCAMTA1GLIS3NKX2-1TEAD4YAP1YWHA (14-3-3)
Complex memberships
TAZ-TEAD transcriptional complex

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 Wwtr1 knockout mice develop glomerulocystic kidney disease with reduced/shorter cilia in cyst-lining cells, and siRNA knockdown of Wwtr1 in mIMCD3 renal collecting duct cells recapitulates loss of cilia integrity and downregulation of cilia-associated genes (Tg737, Kif3a, Dctn5, Pkhd1, Ofd1), establishing Wwtr1 as critical for renal cilia integrity. Homologous recombination knockout mouse, siRNA knockdown in mIMCD3 cells, RT-PCR for cilia genes Proceedings of the National Academy of Sciences of the United States of America High 17251353
2009 Wwtr1/TAZ physically interacts with the transcription factor Glis3 via a P/LPXY motif in the C-terminus of Glis3, and Wwtr1 enhances Glis3-mediated transcriptional activation, functioning as a coactivator; mutations in the P/LPXY motif abrogate both the interaction and Glis3 transcriptional activity. Co-immunoprecipitation, transcriptional reporter assays, site-directed mutagenesis of P/LPXY motif Molecular and cellular biology High 19273592
2012 GSK3 phosphorylates an N-terminal phosphodegron in TAZ/WWTR1, causing phosphorylated TAZ to bind the β-TrCP subunit of the SCF(β-TrCP) E3 ubiquitin ligase, leading to TAZ ubiquitylation and proteasomal degradation. This pathway is activated when PI3K signaling is low (allowing GSK3 activity), and TAZ levels are elevated in PTEN-mutant cells with high PI3K activity. In vitro kinase assay, co-immunoprecipitation, ubiquitylation assay, site-directed mutagenesis of phosphodegron, western blotting in PTEN mutant cancer cells The Journal of biological chemistry High 22692215
2015 The WWTR1(TAZ)-CAMTA1 fusion oncoprotein localizes constitutively to the nucleus (escaping normal cytoplasmic retention/14-3-3 binding/degradation), activates a TAZ-like transcriptional program, confers resistance to anoikis, and induces oncogenic transformation in cells. Subcellular fractionation/immunofluorescence, soft agar colony formation, anoikis resistance assays, transcriptional profiling Oncogene High 25961935
2016 Hepatocyte TAZ/WWTR1 promotes NASH by activating TEAD-dependent transcription of Indian hedgehog (Ihh), a secreted factor that activates fibrogenic genes in hepatic stellate cells; silencing hepatocyte TAZ prevented/reversed hepatic inflammation, hepatocyte death, and fibrosis (but not steatosis) in murine NASH models. Hepatocyte-specific siRNA knockdown and overexpression in mouse NASH models, reporter assays for TEAD-Ihh axis, in vitro/in vivo mechanistic studies Cell metabolism High 28068223
2017 In zebrafish, Wwtr1 (with Yap1) is specifically localized to presumptive epidermis and notochord, and regulates posterior body extension and epidermal fin fold morphogenesis by controlling Fibronectin assembly underneath the presumptive epidermis and surrounding the notochord. Zebrafish loss-of-function (mutant/morpholino), live imaging, immunofluorescence for Fibronectin assembly, tissue-specific localization eLife High 29283341
2018 In zebrafish, Wwtr1 establishes compact wall architecture necessary for cardiac trabeculation; loss of wwtr1 causes disorganized cortical actin and abnormal cell-cell junctions in compact layer cardiomyocytes. Additionally, Nrg/Erbb2 signaling promotes nuclear export of Wwtr1 in cardiomyocytes, negatively regulating its nuclear activity. Zebrafish genetic loss-of-function, mosaic analysis, immunofluorescence for actin/junctions, pharmacological/genetic manipulation of Nrg/Erbb2 signaling, subcellular localization of Wwtr1 Development (Cambridge, England) High 29773645
2018 TAZ/WWTR1 acts as a transcriptional modifier of NKX2-1 in the lung: co-expression of TAZ/WWTR1 restores transactivation of a lung-specific promoter by a C-terminal NKX2-1 mutant (but not an N-terminal mutant), and both NKX2-1 mutants physically interact equally with TAZ/WWTR1; this implicates TAZ in the lung phenotype of brain-lung-thyroid syndrome. Co-immunoprecipitation, luciferase reporter assays, confocal microscopy, site-directed mutagenesis The Journal of clinical endocrinology and metabolism Medium 29294041
2019 TEAD4, YAP1, and WWTR1 directly repress Sox2 transcription prior to the 16-cell stage in mouse embryos, preventing premature activation of pluripotency; this repression is sensitive to LATS kinase activity even though LATS does not normally limit YAP1/WWTR1/TEAD4 activity at these stages. Mouse embryo genetic knockouts (Yap1, Wwtr1, Tead4), reporter assays for direct transcriptional repression of Sox2, pharmacological LATS inhibition Development (Cambridge, England) High 31444221
2021 WWTR1(TAZ)-CAMTA1 expression in endothelial cells is sufficient to drive formation of EHE-like vascular tumors; constitutively active TAZ similarly drives EHE-like tumors. The TAZ-CAMTA1 fusion requires its interaction with TEAD to mediate transformation, as disruption of the TAZ-CAMTA1–TEAD interaction or dominant-negative TEAD expression inhibits tumor formation in vivo. Endothelial-specific conditional mouse model, dominant-negative TEAD expression, genetic disruption of TEAD-binding domain, histological/immunohistochemical characterization Genes & development High 33766984
2021 The WWTR1(TAZ)-CAMTA1 gene fusion knocked into the endogenous Wwtr1 locus by Cre activation is sufficient to drive EHE tumor formation with specificity; activated TAZ produces indistinguishable EHE-like tumors, establishing constitutive TAZ activation as the core oncogenic mechanism. Conditional knock-in mouse model targeting Wwtr1 locus, Cre-activation, histology, immunohistochemistry, genetic analysis Genes & development High 33766982
2021 Zebrafish foxc1a directly binds the wwtr1 promoter at three sites and transcriptionally activates wwtr1 expression; overexpression of wwtr1 mRNA rescues ventricular chamber maturation defects in foxc1a-null embryos, placing wwtr1 as a direct downstream target of Foxc1a in cardiac development. Dual-luciferase assay, chromatin immunoprecipitation (ChIP), mRNA overexpression rescue experiment in zebrafish Journal of genetics and genomics Medium 34923164
2022 SORBS3 depletion increases F-actin structures which compete with YAP1-WWTR1/TAZ for binding to AMOT (angiomotin) proteins in the cytosol; unbound YAP1-WWTR1/TAZ translocates to the nucleus and upregulates target genes (including myosin- and actin-related genes) to promote autophagosome formation. siRNA knockdown of SORBS3, F-actin manipulation, nuclear/cytoplasmic fractionation, autophagosome quantification, gene expression analysis Autophagy Medium 35822241
2022 ZO-2/Tjp2 negatively regulates Yap and Wwtr1/Taz protein expression in hepatocytes; loss of Tjp2 upregulates Yap and Wwtr1/Taz protein, and DDC-diet-induced hepatocyte-to-cholangiocyte transdifferentiation in Tjp2 cKO mice requires Yap and Wwtr1/Taz activity. Liver-specific Tjp2 conditional knockout mice, DDC diet challenge, Western blot for Yap/Taz protein, genetic epistasis (hepatocyte vs. cholangiocyte-specific deletion) NPJ Regenerative medicine Medium 36151109
2022 WWTR1/TAZ nuclear localization mediates mesothelial-mesenchymal transition (MMT) induced by lysophosphatidic acid (LPA) and stiff extracellular matrix; siRNA knockdown of Taz suppressed LPA-induced MMT and MMT on stiff hydrogels. TGF-β1 signaling inhibition did not suppress stiffness-induced MMT, indicating TAZ acts downstream of mechanical signals independently of TGF-β1 in this context. siRNA knockdown of Taz, hydrogels of defined stiffness, immunofluorescence for TAZ nuclear localization, LPA and TGF-β1 treatment, myofibroblast differentiation assays Journal of cellular physiology Medium 35445400
2022 WWTR1 S89W somatic mutation reduces binding of TAZ to 14-3-3 proteins, leading to constitutive nuclear translocation of TAZ, Hippo pathway repression, and acquisition of oncogenic phenotypes (increased proliferation, migration, colony formation, tumorigenesis in vivo); these effects are reversed by YAP/TAZ inhibition with verteporfin. In vitro functional assays (proliferation, migration, colony formation), 14-3-3 binding assay, subcellular fractionation/immunofluorescence, xenograft mouse model, verteporfin treatment The Journal of pathology High 35411948
2022 WWTR1 promotes trophoblast stem cell self-renewal, is required for cytotrophoblast differentiation to extravillous trophoblasts (EVTs), and prevents induction of the syncytiotrophoblast (STB) fate; mechanistically, WWTR1 fine-tunes trophoblast fate by directly regulating WNT signaling components. shRNA knockdown and overexpression in human trophoblast stem cells and primary CTBs, placental explants, single-cell RNA sequencing, mechanistic WNT pathway analysis Proceedings of the National Academy of Sciences of the United States of America High 36037374
2023 Polycystin-1 (PC1) and Wwtr1 have interdependent (additive/cooperative) mechanosensing functions in osteoblasts; double osteoblast-specific conditional knockout of Pkd1 and Wwtr1 shows greater reductions in bone mass, periosteal mineral apposition, and impaired mechanical loading responses than either single KO, and resistance to the anabolic mechanomimetic MS2 requires both genes. Osteoblast-specific conditional double knockout mice, micro-CT, mechanical loading assay, pharmacological mechanomimetic (MS2), gene expression profiling; genetic epistasis Bone research High 37884491
2023 In cardiac myofibroblasts, Yap/Wwtr1 depletion (but not Yap depletion alone) attenuates fibrosis and improves cardiac function post-infarction; Ccn3 is identified as a downstream target of Yap/Wwtr1 in myofibroblasts, and recombinant CCN3 administration aggravates cardiac fibrosis, establishing Ccn3 as a mediator of Yap/Wwtr1-driven adverse cardiac remodeling. Myofibroblast-specific conditional double KO (Yap;Wwtr1;Postn-Cre), myocardial infarction model, scRNA-seq, siRNA knockdown in vitro, recombinant CCN3 administration in vivo Frontiers in cardiovascular medicine High 36998974
2023 Wwtr1-deficient mice display reduced corneal endothelial cell (CEnC) density, abnormal CEnC morphology, softer Descemet's membrane, altered Na/K-ATPase and ZO-1 localization, and impaired CEnC wound healing, modeling Fuchs' endothelial corneal dystrophy; nuclear WWTR1/TAZ protein is elevated and mislocalized surrounding guttae in FECD patients. Wwtr1 knockout mouse model, atomic force microscopy, immunofluorescence, cryoinjury/keratectomy wound healing assay, human CEnC analysis Investigative ophthalmology & visual science Medium 37074694
2023 Wnt16 promotes vascular smooth muscle contractile phenotype via Taz (Wwtr1) activation; siRNA targeting Taz (but not Yap1) phenocopies Wnt16 deficiency, Taz siRNA inhibits contractile gene upregulation by Wnt16, and Wnt16 stimulates Taz binding to Acta2 chromatin with H3K4me3 methylation; TEAD cognates in the Acta2 promoter are required for transcriptional responses to Wnt16/Taz. siRNA knockdown, ChIP assay, promoter reporter assay, verteporfin inhibition, mitochondrial respiration assay, mouse genetic model Endocrinology Medium 38123514
2023 WWTR1/TAZ nuclear localization is required for sensitization of p53-proficient colorectal cancer cells to oxaliplatin; nuclear TAZ accumulates following oxaliplatin-induced core Hippo pathway downregulation and is required for increased sensitivity in an effect independent of p73 but dependent on nuclear relocalization and p53 status. Loss-of-function (siRNA/drug), nuclear fractionation, co-treatment with YAP/TAZ inhibitors (verteporfin, CA3), multiple colorectal cell lines with known p53 status BMC cancer Medium 38741073
2024 WWTR1 transcriptionally upregulates TGF-β receptor type II (TβRII) expression by directly binding its promoter in osteoblasts; IFT20 stabilizes TβRII protein by blocking c-Cbl-mediated ubiquitination; double deletion of IFT20 and Wwtr1 in osteoblasts synergistically inhibits osteogenesis and promotes adipogenesis and osteoclastogenesis. Conditional double knockout mice, chromatin immunoprecipitation (ChIP), ubiquitination assay, Co-immunoprecipitation, OVX/HFD osteoporosis models, gene expression analysis Research square (preprint)preprint Medium 38562782
2024 The novel WWTR1::TFE3 fusion protein promotes colony formation in soft agar (oncogenic transformation); this transformative effect requires the WWTR1 domain's ability to bind TEAD transcription factors, as mutation of the TEAD-binding domain of WWTR1 in the fusion abrogates transformation. Soft agar colony formation assay in NIH3T3 cells, site-directed mutagenesis of TEAD-binding domain of WWTR1 portion Genes, chromosomes & cancer Medium 38380774
2026 Wwtr1 (TAZ) deficiency in corneal endothelial cells leads to progressive ER stress, mitochondrial structural and functional abnormalities, impaired Na+/K+ ATPase localization, and age-dependent dysregulation of autophagy and extracellular matrix organization genes, establishing a mechanistic link between disrupted mechanotransduction and organelle stress in CEnC degeneration. Single-cell transcriptomics (scRNA-seq), transmission electron microscopy, immunofluorescence, Wwtr1 knockout mouse at two age points bioRxiv (preprint)preprint Medium 41756894

Source papers

Stage 0 corpus · 63 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 A novel WWTR1-CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes, chromosomes & cancer 397 21584898
2016 Hepatocyte TAZ/WWTR1 Promotes Inflammation and Fibrosis in Nonalcoholic Steatohepatitis. Cell metabolism 346 28068223
2007 Glomerulocystic kidney disease in mice with a targeted inactivation of Wwtr1. Proceedings of the National Academy of Sciences of the United States of America 252 17251353
2012 The N-terminal phosphodegron targets TAZ/WWTR1 protein for SCFβ-TrCP-dependent degradation in response to phosphatidylinositol 3-kinase inhibition. The Journal of biological chemistry 137 22692215
2015 miR-9-3p plays a tumour-suppressor role by targeting TAZ (WWTR1) in hepatocellular carcinoma cells. British journal of cancer 96 26125451
2015 Mechanism of action of a WWTR1(TAZ)-CAMTA1 fusion oncoprotein. Oncogene 92 25961935
2009 Glis3 is associated with primary cilia and Wwtr1/TAZ and implicated in polycystic kidney disease. Molecular and cellular biology 89 19273592
2015 Thoracic epithelioid malignant vascular tumors: a clinicopathologic study of 52 cases with emphasis on pathologic grading and molecular studies of WWTR1-CAMTA1 fusions. The American journal of surgical pathology 85 25353289
2021 WWTR1(TAZ)-CAMTA1 gene fusion is sufficient to dysregulate YAP/TAZ signaling and drive epithelioid hemangioendothelioma tumorigenesis. Genes & development 59 33766982
2010 TAZ/WWTR1 is overexpressed in papillary thyroid carcinoma. European journal of cancer (Oxford, England : 1990) 59 21131195
2015 Molecular characterization of epithelioid haemangioendotheliomas identifies novel WWTR1-CAMTA1 fusion variants. Histopathology 58 25817592
2016 Expanding the molecular signature of ossifying fibromyxoid tumors with two novel gene fusions: CREBBP-BCORL1 and KDM2A-WWTR1. Genes, chromosomes & cancer 57 27537276
2016 Statin attenuates cell proliferative ability via TAZ (WWTR1) in hepatocellular carcinoma. Medical oncology (Northwood, London, England) 50 27734263
2021 WWTR1(TAZ)-CAMTA1 reprograms endothelial cells to drive epithelioid hemangioendothelioma. Genes & development 46 33766984
2020 Variant WWTR1 gene fusions in epithelioid hemangioendothelioma-A genetic subset associated with cardiac involvement. Genes, chromosomes & cancer 46 32170768
2019 Fusion of the Genes WWTR1 and FOSB in Pseudomyogenic Hemangioendothelioma. Cancer genomics & proteomics 44 31243110
2019 TEAD4, YAP1 and WWTR1 prevent the premature onset of pluripotency prior to the 16-cell stage. Development (Cambridge, England) 44 31444221
2016 The Hippo effector TAZ (WWTR1) transforms myoblasts and TAZ abundance is associated with reduced survival in embryonal rhabdomyosarcoma. The Journal of pathology 39 27184927
2022 Hippo signaling cofactor, WWTR1, at the crossroads of human trophoblast progenitor self-renewal and differentiation. Proceedings of the National Academy of Sciences of the United States of America 36 36037374
2017 Regulation of posterior body and epidermal morphogenesis in zebrafish by localized Yap1 and Wwtr1. eLife 34 29283341
2018 The Hippo pathway effector Wwtr1 regulates cardiac wall maturation in zebrafish. Development (Cambridge, England) 32 29773645
2017 YAP and WWTR1: New targets for skin cancer treatment. Cancer letters 31 28279717
2023 YAP1 and WWTR1 expression inversely correlates with neuroendocrine markers in Merkel cell carcinoma. The Journal of clinical investigation 26 36719743
2023 Loss of CDKN2A Cooperates with WWTR1(TAZ)-CAMTA1 Gene Fusion to Promote Tumor Progression in Epithelioid Hemangioendothelioma. Clinical cancer research : an official journal of the American Association for Cancer Research 24 36598859
2019 The Hippo signaling effector WWTR1 is a metastatic biomarker of gastric cardia adenocarcinoma. Cancer cell international 19 30976198
2012 Lentivirus-mediated RNA interference targeting WWTR1 in human colorectal cancer cells inhibits cell proliferation in vitro and tumor growth in vivo. Oncology reports 14 22470139
2019 Overexpression of lncRNA WWTR1-AS1 associates with tumor aggressiveness and unfavorable survival in head-neck squamous cell carcinoma. Journal of cellular biochemistry 13 31172583
2024 Epithelioid hemangioendothelioma (EHE) with WWTR1::TFE3 gene fusion, a novel fusion variant. Genes, chromosomes & cancer 12 38380774
2023 Genetic interactions between polycystin-1 and Wwtr1 in osteoblasts define a novel mechanosensing mechanism regulating bone formation in mice. Bone research 11 37884491
2023 Myofibroblast Ccn3 is regulated by Yap and Wwtr1 and contributes to adverse cardiac outcomes. Frontiers in cardiovascular medicine 10 36998974
2022 ZO-2/Tjp2 suppresses Yap and Wwtr1/Taz-mediated hepatocyte to cholangiocyte transdifferentiation in the mouse liver. NPJ Regenerative medicine 10 36151109
2021 Pseudomyogenic hemangioendothelioma of bone with rare WWTR1-FOSB fusion gene: Case report and literature review. Clinical case reports 10 33768875
2018 TAZ/WWTR1 Mediates the Pulmonary Effects of NKX2-1 Mutations in Brain-Lung-Thyroid Syndrome. The Journal of clinical endocrinology and metabolism 10 29294041
2022 Increased SORBS3 expression in brain ageing contributes to autophagic decline via YAP1-WWTR1/TAZ signaling. Autophagy 8 35822241
2023 Mice Deficient in TAZ (Wwtr1) Demonstrate Clinical Features of Late-Onset Fuchs' Endothelial Corneal Dystrophy. Investigative ophthalmology & visual science 7 37074694
2022 A novel WWTR1::AFF2 fusion in an intra-abdominal soft tissue sarcoma with associated endometriosis. Genes, chromosomes & cancer 7 35429182
2021 Cell type-specific YAP1-WWTR1/TAZ transcriptional responses after autophagy perturbations are determined by levels of α-catenins (CTNNA1 and CTNNA3). Autophagy 7 34036899
2021 Zebrafish Foxc1a controls ventricular chamber maturation by directly regulating wwtr1 and nkx2.5 expression. Journal of genetics and genomics = Yi chuan xue bao 6 34923164
2014 WWTR1 (WW domain containing transcription regulator 1). Atlas of genetics and cytogenetics in oncology and haematology 6 26366208
2024 The Hippo pathway terminal effector TAZ/WWTR1 mediates oxaliplatin sensitivity in p53 proficient colon cancer cells. BMC cancer 5 38741073
2022 A Novel Cryptic t(2;3)(p21;q25) Translocation Fuses the WWTR1 and PRKCE Genes in Uterine Leiomyoma With 3q- as the Sole Visible Chromosome Abnormality. Cancer genomics & proteomics 5 35985686
2020 Fluorescence in situ hybridization for WWTR1-CAMTA1 has higher sensitivity and specificity for epithelioid hemangioendothelioma diagnosis. American journal of translational research 5 32913529
2019 Generation of a WWTR1 mutation induced pluripotent stem cell line, MUSIi012-A-1, using CRISPR/Cas9. Stem cell research 5 31677525
2018 A Case of Large Meningeal Epithelioid Hemangioendothelioma With WWTR1-CAMTA1 Gene Rearrangement and Slow Growth Over 15 Years. Journal of neuropathology and experimental neurology 5 30085199
2023 Wnt16 Promotes Vascular Smooth Muscle Contractile Phenotype and Function via Taz (Wwtr1) Activation in Male LDLR-/- Mice. Endocrinology 4 38123514
2022 Recurrent WWTR1 S89W mutations and Hippo pathway deregulation in clear cell carcinomas of the cervix. The Journal of pathology 4 35411948
2017 Effect and mechanism of RNAi targeting WWTR1 on biological activity of gastric cancer cells SGC7901. Molecular medicine reports 4 29207147
2025 Skin-analogue primary poroid neoplasms of the head and neck with YAP1/WWTR1::MAML2/NUTM1 fusions: clinicopathologic and genetic spectrum of a novel tumor family delineated in a series of 10 cases. Virchows Archiv : an international journal of pathology 3 41350449
2022 DNA-damage induced cell death in yap1;wwtr1 mutant epidermal basal cells. eLife 3 35635436
2024 Uncovering the relationship between YAP/ WWTR1 (TAZ) genes expression and LncRNAs of SNHG15, HCP5 and LINC01433 in breast cancer tissues. Pathology, research and practice 2 38599044
2024 Uncovering the WWTR1::NCOA2 Gene fusion in low-grade myoepithelial-rich neoplasm with HMGA2 expression: A case report. Genes, chromosomes & cancer 2 38747338
2024 Primary pulmonary epithelioid hemangioendothelioma metastatic to the pleura and mediastinal lymph node with a prominent rhabdoid cytomorphology showing CAMTA1::WWTR1 fusion and novel PRDM1 and TNFRSF14 mutations. Cytopathology : official journal of the British Society for Clinical Cytology 2 38943251
2022 TAZ/WWTR1 mediates liver mesothelial-mesenchymal transition induced by stiff extracellular environment, TGF-β1, and lysophosphatidic acid. Journal of cellular physiology 2 35445400
2019 Epithelioid Hemangioendothelioma Arising Within Mediastinal Myelolipoma: A WWTR1-Driven Composite Neoplasm. International journal of surgical pathology 2 30942102
2025 YAP1 and WWTR1 are required for murine pregnancy initiation. Reproduction (Cambridge, England) 1 39503541
2024 IFT20 and WWTR1 govern bone homeostasis via synchronously regulating the expression and stability of TβRII in osteoblast lineage cells. Research square 1 38562782
2022 A Rare Case of Primary Epithelioid Hemangioma of Bone with WWTR1::FOSB Fusion: A Benign Lesion with the Potential to Mimic Malignancy. International journal of surgical pathology 1 35946109
2026 TAZ (Wwtr1) deficiency leads to ER stress and mitochondrial dysfunction in a mouse model of Fuchs' endothelial corneal dystrophy. bioRxiv : the preprint server for biology 0 41756894
2025 A novel bispecific siRNA concept: Efficient dual knockdown of YAP1 and WWTR1 with a single guide strand. Molecular therapy. Nucleic acids 0 41341748
2024 LncRNA WWTR1-AS1 upregulates Notch3 through miR-136 to increase cancer cell stemness in cervical squamous cell carcinoma. BMC women's health 0 38331752
2024 Yes Associated Transcriptional Regulator 1 (YAP1) and WW Domain Containing Transcription Regulator (WWTR1) are required for murine pregnancy initiation. bioRxiv : the preprint server for biology 0 38766130
2023 Spontaneous urinary bladder regeneration after subtotal cystectomy increases YAP/WWTR1 signaling and downstream BDNF expression: Implications for smooth muscle injury responses. PloS one 0 37494380
2021 Novel detection of the CAMTA1-WWTR1 fusion gene in extra-adrenal myelolipoma-like lesion: a case report. Virchows Archiv : an international journal of pathology 0 34231054

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