Affinage

YAP1

Transcriptional coactivator YAP1 · UniProt P46937

Length
504 aa
Mass
54.5 kDa
Annotated
2026-06-11
100 papers in source corpus 41 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

YAP1 is a transcriptional coactivator that converts mechanical, developmental, and growth-factor cues into target-gene programs governing tissue growth, cell fate, and tumorigenesis (PMID:11358867, PMID:16354681). Its central output is a complex with TEAD/TEF transcription factors: YAP1 supplies the transcriptional activation domain through an N-terminal TEAD-binding domain that engages all four TEAD paralogs, and both TEAD interaction and TEAD DNA binding are required for activation, while excess YAP1 is sequestered in the cytoplasm with 14-3-3 (PMID:11358867). This TEAD-dependent activity drives diverse programs including endothelial mitochondrial biogenesis and angiogenesis via PGC1α (PMID:29680477), DNMT1-mediated hepatocyte-to-biliary reprogramming (PMID:35550144), and oncogenic outputs such as CALM2/SLC2A1 induction (PMID:34990589) and PD-L1 transcription via a YAP1/TFCP2 complex (PMID:38583649); YAP1/TEAD can also act repressively, silencing Sox2 to restrain premature pluripotency (PMID:31444221) and attenuating NODAL/FOXH1 to pattern germ layers (PMID:35063126). YAP1 nuclear access is set by the Hippo cascade: LATS1-site phosphorylation, including the inhibitory S127 mark, increases YAP1 nuclear export and cytoplasmic retention, and constitutively active phospho-site mutants (S127A, 5SA) escape this control (PMID:34060624, PMID:30918126). Layered onto this, YAP1 abundance is tuned by ubiquitin ligases and deubiquitinases (STUB1-mediated K48 ubiquitination at K280 (PMID:31393050); stabilization by ATXN3, OTUD7B, OTUD5, and TRAF6-mediated K63 linkage (PMID:37818078, PMID:37429790, PMID:39293571, PMID:38583649)), by CBX4 SUMOylation at K97/K280 that competes with S127 phosphorylation (PMID:39154499), by NEK1 phosphorylation at Y407 (PMID:36979713), and by a Hippo-independent matrix-softness route in which PTEN-driven lysosomal cathepsin L directly digests YAP1 (PMID:39460766), as well as by mRNA-level control through ENO1 translation and METTL14/m6A decay (PMID:37500770, PMID:39563370). Beyond TEAD, YAP1 engages Smad7 to potentiate TGF-β inhibition (PMID:12118366), RUNX2 to drive transformation (PMID:17438369), and Angiomotin/AMOTL1, the latter supporting a TEAD-independent, S6-kinase-linked role in dendritic morphogenesis (PMID:32313226, PMID:31042703). Germline knockout establishes essential roles in yolk-sac vasculogenesis, chorioallantoic fusion, and axis elongation (PMID:16354681), and oncogenic YAP1 fusions (YAP1-MAML2, YAP1-NUTM1) act through constitutive, Hippo-resistant TEAD-dependent transcription sufficient to induce tumors (PMID:31145701, PMID:36008139).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Established YAP1's first molecular partnership, defining it as an SH3-binding adaptor before any transcriptional role was known.

    Evidence Anti-idiotypic antibody screen and peptide-competition co-IP identifying binding to the Yes SH3 domain via a proline-rich motif

    PMID:8035999

    Open questions at the time
    • Did not reveal a transcriptional or signaling function
    • Functional consequence of SH3 binding in cells not established
  2. 2001 High

    Defined YAP1's core function as the transcriptional activation module of TEAD factors, explaining how it drives gene expression.

    Evidence Protein purification, co-IP with all four TEAD paralogs, domain mapping, and reporter assays plus cytoplasmic 14-3-3 sequestration

    PMID:11358867

    Open questions at the time
    • Upstream signals controlling the TEAD/14-3-3 balance not yet defined
    • Genome-wide TEAD target set not mapped
  3. 2002 High

    Showed YAP1 cross-talks with TGF-β signaling beyond TEAD, broadening its interactome to Smad regulation.

    Evidence Yeast two-hybrid, co-IP, and reporter assays with dominant-negative YAP1(1-301) potentiating Smad7-TGFβRI association

    PMID:12118366

    Open questions at the time
    • Physiological context of Smad7 potentiation unclear
    • Relationship to TEAD activity not addressed
  4. 2006 High

    Established YAP1 as essential in vivo for early development, moving it from biochemistry to organismal requirement.

    Evidence Germline Yap knockout in mice with vasculogenesis, chorioallantoic, and axis-elongation defects at E8.5

    PMID:16354681

    Open questions at the time
    • Did not separate TEAD-dependent from -independent contributions
    • Cell-autonomous vs non-autonomous roles unresolved
  5. 2007 High

    Linked YAP1 to oncogenic transformation through a defined partner, identifying RUNX2 as a transformation cofactor.

    Evidence Co-IP, RUNX2 P409A binding mutant, and soft-agar/foci transformation assays

    PMID:17438369

    Open questions at the time
    • Direct target genes of the YAP1-RUNX2 complex not defined
    • In vivo relevance not tested
  6. 2016 Medium

    Connected YAP1 to mechano-fibrotic signaling and metabolic regulation, expanding its physiological roles.

    Evidence Integrin-β1/PAK myofibroblast assays and in vivo YAP1 inhibition (fibrosis); MST1-YAP1-TEAD1 RNAi axis controlling GLUT1/C-MYC; miR-375/ZEB1 circuit

    PMID:27270433 PMID:27535340 PMID:27793648

    Open questions at the time
    • Direct vs indirect transcriptional targets in metabolism not fully resolved
    • Context-dependence of positive vs negative C-MYC regulation unexplained
  7. 2018 Medium

    Mechanistically dissected how nuclear YAP1/TEAD drives angiogenic and EMT programs through specific effectors.

    Evidence YAP1-S127A/S94A mutants and PGC1α knockdown (angiogenesis); CDK8/19 and matrix-rigidity-dependent SMAD1-driven EMT; YAP1-AP-1 cooperation in osteoclastogenesis; Tie2 regulation in endothelium

    PMID:29432919 PMID:29680477 PMID:29780169 PMID:30156429

    Open questions at the time
    • Tissue-specific selection of distinct effector genes not explained
    • Direct vs indirect target status of several effectors not established
  8. 2019 High

    Revealed YAP1 protein-level control by ubiquitin ligases and stabilizing partners, and TEAD-independent functions.

    Evidence STUB1 K48 ubiquitination at K280; BRCA1-NF2-Hippo axis with YAP1-5SA rescue; AMOTL1 cytoplasmic stabilization; Amot-YAP1 S6-kinase-linked dendritic morphogenesis; fusion oncoprotein associations (FUS-DDIT3, YAP1-MAML2/NUTM1)

    PMID:30898787 PMID:30918126 PMID:31042703 PMID:31145701 PMID:31393050 PMID:32313226

    Open questions at the time
    • Hierarchy among competing stabilizing/destabilizing inputs unclear
    • How TEAD-independent (S6K) signaling is selected over canonical output not defined
  9. 2019 Medium

    Established YAP1/TEAD as a transcriptional repressor in developmental fate decisions, not only an activator.

    Evidence Yap1/Wwtr1/Tead4 KO embryos with LATS-sensitive direct Sox2 repression; granulosa cell conditional KO phenotypes

    PMID:31199671 PMID:31444221

    Open questions at the time
    • Molecular basis for switch between activation and repression unresolved
    • Co-repressor identity not defined
  10. 2020 High

    Placed YAP1 within a stress-responsive inflammatory pathway, linking DNA-damage signaling to cytokine output.

    Evidence Mouse telomere-dysfunction models with ATM/c-ABL-YAP1-pro-IL-18 axis, pharmacological inhibition, and patient tissue validation

    PMID:32958778

    Open questions at the time
    • Whether IL-18 induction is TEAD-dependent not specified
    • Direct YAP1 binding at the IL-18 locus not shown
  11. 2021 High

    Quantified the kinetic basis of Hippo regulation, showing LATS phosphorylation acts on nuclear export rather than import.

    Evidence Optogenetic LOV sequestration with live-cell and lattice light-sheet imaging measuring YAP1 shuttling rates

    PMID:34060624

    Open questions at the time
    • Molecular export machinery engaged by phospho-YAP1 not identified
    • Generalizability across cell types not tested
  12. 2022 High

    Demonstrated that YAP1 activity alone is sufficient to drive and maintain tumors, and validated direct TEAD-targeting chemistry.

    Evidence YAP1-MAML2 and constitutively active YAP1(S127/397A) mouse meningioma induction; conditional YAP1 knockdown causing mesothelioma regression; covalent cyanamide TEAD palmitate-pocket inhibitors with TEAD2 co-crystals

    PMID:35689194 PMID:36008139 PMID:36562717

    Open questions at the time
    • Determinants of Hippo-dependent vs -independent tumor reliance not fully defined
    • Long-term resistance mechanisms to TEAD inhibitors unaddressed
  13. 2022 High

    Mapped both upstream transcriptional control of the YAP1 gene and key downstream effector targets driving its programs.

    Evidence CIC repression of YAP1 transcription via GGAA motifs; PTPN14-LATS1 axis (HPV E7) controlling YAP1 nuclear localization; YAP1/TEAD-DNMT1 hepatocyte reprogramming (ChIP-seq); CALM2/SLC2A1 rescue screen; NODAL/FOXH1 repression in gastruloids

    PMID:34990589 PMID:35063126 PMID:35170430 PMID:35550144 PMID:36198276 PMID:39248565

    Open questions at the time
    • Integration of multiple upstream inputs into a single output not modeled
    • Tissue specificity of effector selection unresolved
  14. 2023 Medium

    Expanded post-transcriptional and post-translational tuning of YAP1 abundance through deubiquitinases and mRNA regulation.

    Evidence ATXN3 (WW-domain binding) and OTUD7B deubiquitination stabilizing YAP1; ENO1 CUG-element binding promoting YAP1 translation; YAP1-miR-21-5p-PGR repressive axis (ChIP-PCR, RNA-IP)

    PMID:37071897 PMID:37429790 PMID:37500770 PMID:37818078

    Open questions at the time
    • Relative contribution of each regulator in normal physiology unclear
    • Single-lab co-IP/ubiquitination findings without reciprocal cross-validation
  15. 2024 Medium

    Defined additional non-canonical regulatory inputs to YAP1 stability and activity spanning SUMO, tyrosine phosphorylation, K63 ubiquitination, lysosomal degradation, and m6A decay.

    Evidence CBX4 SUMOylation at K97/K280 competing with S127; NEK1 Y407 phosphorylation cascade; TRAF6 K63 ubiquitination enabling YAP1/TFCP2-PD-L1; PTEN-cathepsin L lysosomal degradation under soft matrix (in vitro reconstitution); METTL14/m6A-YTHDF2 transcript decay; OTUD5 stabilization (dapagliflozin)

    PMID:36979713 PMID:38583649 PMID:39154499 PMID:39293571 PMID:39460766 PMID:39563370

    Open questions at the time
    • How these inputs are integrated and prioritized in a given cell unresolved
    • Several mechanisms rest on single-lab evidence

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how the convergent layers of YAP1 control — Hippo phosphorylation, multiple ubiquitin/SUMO and mRNA inputs, and partner choice — are quantitatively integrated to select between activating vs repressive, TEAD-dependent vs -independent outputs in a given cell context.
  • No unified model linking regulatory input strength to specific transcriptional output
  • Determinants of TEAD-dependent vs S6-kinase-linked function not defined
  • Logic of activation vs repression at target loci unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0060089 molecular transducer activity 2 GO:0140097 catalytic activity, acting on DNA 2
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 3
Pathway
R-HSA-392499 Metabolism of proteins 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-162582 Signal Transduction 2
Partners
AMOTL1ATXN3CBX4RUNX2SMAD7STUB1TEAD1TRAF6
Complex memberships
Angiomotin/AMOTL1-YAP1 complexYAP1-TEAD transcriptional complexYAP1/TFCP2 complex

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 YAP65 (YAP1) was identified as a novel protein that binds the SH3 domain of the Yes proto-oncogene product via a proline-rich motif (PVKQPPPLAP). Competition assays with synthetic peptides confirmed the involvement of this proline-rich sequence. YAP65 also bound SH3 domains of Nck, Crk, Src, Abl, and GAP. Anti-idiotypic antibody screen, co-immunoprecipitation, competition assays with synthetic peptides Oncogene High 8035999
2001 YAP65 functions as a transcriptional coactivator for TEAD/TEF transcription factors: it interacts specifically with the C-terminus of all four TEAD proteins via a novel TEAD-binding domain at its N-terminus, provides the transcriptional activation domain for TEAD-dependent transcription, and accumulates in the cytoplasm as a complex with 14-3-3 when in excess. Both TEAD interaction and DNA binding by TEAD were required for transcriptional activation. Protein purification, co-immunoprecipitation, transcriptional reporter assays, subcellular fractionation, overexpression/squelching experiments Genes & development High 11358867
2002 YAP65 interacts with Smad7 (identified by yeast two-hybrid and confirmed by co-IP in COS-7 cells), potentiates Smad7's inhibitory activity against TGF-β/Smad3/4-dependent transcription, and augments the association of Smad7 with activated TGF-β receptor type I. A dominant-negative YAP65(1-301) reduced Smad7-TGFβRI interactions. Yeast two-hybrid screen, co-immunoprecipitation, transcriptional reporter assays, dominant-negative constructs Oncogene High 12118366
2006 Homozygous knockout of Yap in mice causes developmental arrest at ~E8.5 with defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation, establishing essential in vivo roles for YAP1 in these developmental processes. Targeted gene disruption in mice, histology, PECAM1 immunostaining, alpha-globin expression analysis Molecular and cellular biology High 16354681
2007 RUNX2 associates with YAP65 via a PPPY proline-rich motif in its C-terminal domain. Co-expression of RUNX2 and YAP65 synergistically promotes foci formation and anchorage-independent growth. A RUNX2(P409A) mutant that cannot bind YAP65 fails to cooperate with YAP65 in transformation. YAP65 overexpression prevented RUNX2-dependent downregulation of p21(CIP1). Co-immunoprecipitation, site-directed mutagenesis (RUNX2 P409A), soft agar/foci formation assays, luciferase reporter assays, DNA precipitation Cancer biology & therapy High 17438369
2016 In liver myofibroblasts, integrin beta-1 signaling activates PAK proteins and YAP-1 as core pro-fibrotic mediators. YAP-1 is capable of perpetuating integrin beta-1 expression (positive feedback loop). Pharmacological inhibition of YAP-1 in vivo attenuates liver fibrosis. In vitro myofibroblast assays, in vivo pharmacological inhibition, gene knockdown Nature communications Medium 27535340
2016 YAP1 was identified as a direct target of miR-375 in prostate cancer. Knockdown of YAP1 phenocopied miR-375 overexpression (inhibiting invasion and migration), and overexpression of YAP1 rescued anti-invasive effects of miR-375. The ZEB1 transcription factor directly represses miR-375 transcription, placing YAP1 downstream of a ZEB1-miR-375-YAP1 regulatory circuit controlling epithelial plasticity. miRNA target validation, siRNA knockdown, rescue overexpression, invasion/migration assays, multiple patient cohort analysis Oncogene Medium 27270433
2018 YAP1/TEAD1 signaling induces mitochondrial biogenesis in endothelial cells and stimulates angiogenesis through PGC1α. A YAP1-S127A constitutively active mutant increased PGC1α expression and mitochondrial biogenesis; a YAP1-S94A mutant that fails to bind TEAD1 attenuated these effects. PGC1α knockdown inhibited YAP1-S127A-induced EC sprouting and vascular morphogenesis. Constitutively active and binding-deficient YAP1 mutants, TEAD1 knockdown, PGC1α knockdown, in vitro EC sprouting assays, in vivo fibrin gel vascular morphogenesis Microvascular research Medium 29680477
2018 CDK8/19 kinase coordinates BMP4-induced EMT in a YAP1-dependent manner. Both genetic and pharmacological inhibition of CDK8/19 abrogated BMP-induced EMT, nuclear YAP1 localization, and tumor cell invasion. YAP1 activity was required for SMAD1-driven EMT in a matrix-rigidity-dependent manner. Genetic inhibition (siRNA), pharmacological inhibition, RNA-seq meta-analysis, in vitro invasion assays, in vivo syngeneic EMT model Oncogene Medium 29780169
2018 YAP1 interacts with TEAD transcription factors (TEADs) and AP-1, and this cooperative interaction on downstream gene transcription is required for osteoclastogenesis. Verteporfin (which inhibits YAP1-TEAD association) suppressed osteoclast formation and bone resorption. RANKL-induced NF-κB signaling was impaired when YAP1 was inhibited. shRNA-mediated knockdown, verteporfin pharmacological inhibition, co-immunoprecipitation, gene expression analysis, osteoclast differentiation assays Bone Medium 29432919
2019 STUB1 (E3 ubiquitin ligase) ubiquitinates YAP1 at K280 via K48-linked polyubiquitination, leading to YAP1 degradation. This suppresses cancer cell survival and chemoresistance. Low STUB1 expression correlates with increased YAP1 protein in gastric cancer. Co-immunoprecipitation, ubiquitination assays with site-specific mutants (K280), protein stability assays, cell viability assays Cancer science Medium 31393050
2019 BRCA1 facilitates YAP1 protein stabilization and Hippo pathway inactivation through ubiquitination of NF2. In BRCA1-deficient cells, Hippo pathway is turned on. A YAP1-5SA mutant (alanine substitutions at LATS1 recognition sites) resists degradation and rescues YAP1 transcriptional activity in BRCA1-deficient cells, and promotes EGF-independent proliferation and tumorigenesis. BRCA1 KO cells, YAP1 phosphorylation site mutagenesis (5SA/6SA mutants), ubiquitination assays, proliferation and tumorigenesis assays Proceedings of the National Academy of Sciences of the United States of America Medium 30918126
2019 FUS-DDIT3 fusion oncoprotein promotes YAP1 expression, nuclear localization, and transcriptional activity in myxoid liposarcoma cells, and physically associates with YAP1 in the nucleus. Pharmacologic inhibition of YAP1 impairs MLS cell growth in vitro and in vivo. Co-immunoprecipitation (nuclear fractionation), functional genomic screen, pharmacological inhibition, in vivo xenograft EMBO molecular medicine Medium 30898787
2019 AMOTL1 (Angiomotin Like 1) interacts with YAP1 in the cytoplasm and protects YAP1 from ubiquitin-mediated degradation. This interaction promotes YAP1 nuclear translocation to activate downstream targets such as CTGF. Knockdown of AMOTL1 impairs its oncogenic properties and reduces YAP1 protein levels. Co-immunoprecipitation, immunofluorescence, shRNA knockdown, ubiquitination assays Oncogene Medium 32313226
2019 Angiomotin (Amot) and YAP1 form a complex critical for dendritic morphogenesis in hippocampal and Purkinje cells. Conditional deletion of Amot and Yap1 in neurons decreased Purkinje cell dendritic tree complexity and impaired motor coordination. This function does not rely on TEAD interactions or Hippo-dependent gene expression, but instead involves phosphorylation of S6 kinase and S6 ribosomal protein. Conditional neuronal knockout mice, in vitro hippocampal cultures, co-immunoprecipitation, phosphorylation assays, behavioral tests PLoS biology High 31042703
2019 YAP1 fusions (YAP1-MAML2 and YAP1-NUTM1) in poromas strongly transactivate a TEAD reporter and promote anchorage-independent growth. Immunohistochemical staining showed nuclear expression of the N-terminal YAP1 portion with loss of the C-terminal portion, consistent with constitutive nuclear YAP1 activity in these fusion proteins. RNA sequencing, RT-PCR, FISH, immunohistochemistry, TEAD reporter assay, anchorage-independent growth assay The Journal of clinical investigation High 31145701
2019 YAP1 interacts with epidermal growth factor receptor and TGF-β signaling pathways to regulate granulosa cell proliferation, differentiation, and survival. Nuclear (active) YAP1 is predominant in proliferative granulosa cells; cytoplasmic (inactive) YAP1 is in luteinized cells. Foxl2 promoter-driven knockout of Yap1 caused increased granulosa cell apoptosis, decreased corpora lutea, reduced ovarian size, and subfertility. Conditional knockout mice (Foxl2-Cre and Cyp19a1-Cre), in vitro pharmacological inhibition, co-IP, subcellular localization analysis FASEB journal Medium 31199671
2019 YAP1 directly represses Sox2 expression in early mouse embryos, preventing premature pluripotency onset prior to the 16-cell stage. This repression is sensitive to LATS kinase activity. TEAD4, YAP1, and WWTR1 together mediate direct transcriptional repression of Sox2. Yap1/Wwtr1/Tead4 knockout mouse embryos, gene expression analysis, genetic epistasis with LATS kinase inhibition Development (Cambridge, England) Medium 31444221
2020 Telomere dysfunction activates YAP1 via pATM/c-ABL-mediated signaling, upregulating pro-IL-18 expression in intestinal epithelium. Pharmacological inhibition of ATM or YAP1 dramatically reduces IL-18 and intestinal inflammation in mice with telomere dysfunction. This establishes a telomere dysfunction-ATM-YAP1-pro-IL-18 inflammatory pathway. Mouse telomere dysfunction models, pharmacological inhibition (ATM, YAP1, caspase-1 inhibitors), antibiotics treatment, patient biopsy analysis (γH2AX, YAP1, IL-18) Nature communications High 32958778
2021 Phosphorylation of YAP1 on canonical LATS1 sites enhances its rate of nuclear export (not entry). YAP1 import and export rates correlate within the same cell. YAP1 and TAZ rates of nuclear entry and exit are also correlated with each other. Optogenetic LOV-domain mitochondria sequestration system with blue-light release, live-cell fluorescence imaging, quantitative nuclear/cytoplasmic flux analysis, lattice light-sheet microscopy Journal of cell science High 34060624
2021 YAP1-MAML2 fusion primarily functions via TEAD-dependent YAP activity that is resistant to Hippo signaling. Expression of YAP1-MAML2 in mice induces meningioma-like tumors resembling NF2 mutant meningiomas. Constitutively active YAP1(S127/397A) alone is sufficient to induce similar tumors, indicating the YAP component drives oncogenesis. YAP-TEAD inhibitors inhibit viability of YAP1-MAML2-driven tumors ex vivo. Mouse tumor models, gene expression profiling, YAP-TEAD inhibitor treatment (ex vivo), constitutively active YAP1 expression, epistasis with Hippo signaling Genes & development High 36008139
2022 HPV E7 activates YAP1 nuclear localization in basal epithelial cells by binding and degrading PTPN14 tumor suppressor. YAP1 transcriptional activity is required for E7 to extend primary keratinocyte lifespan. YAP1 activation by E7 causes cells to be retained in the basal compartment of stratified epithelia. HPV E7 expression, PTPN14 knockout, YAP1 nuclear localization assays, primary keratinocyte lifespan assays, stratified epithelium models eLife High 35170430
2022 HPV18 E7 degrades PTPN14, which decreases phosphorylation of LATS1 T1079 (active form) and YAP1 S127 (inhibitory phosphorylation). PTPN14-dependent differentiation requires LATS kinases and PTPN14 PPxY motifs. MST1/2 kinases and PTPN14 phosphatase activity are not required for PTPN14 to promote differentiation, establishing that PTPN14 acts upstream of LATS1 to inhibit YAP1. PTPN14 knockout, HPV18 E7 expression, LATS1 phosphorylation assays, YAP1 S127 phosphorylation assays, domain mutagenesis (PPxY motifs, phosphatase active site) mBio High 39248565
2022 YAP1-TEAD complex activates DNMT1 expression, which directs hepatocyte-to-biliary epithelial cell fate switch through repression of hepatocyte-specific genes. DNMT1 re-expression restores ICC development following TEAD repression, establishing DNMT1 as a downstream effector of YAP1/TEAD in hepatocyte reprogramming. Sleeping beauty/hydrodynamic tail vein injection ICC model, Yap1/Sox9 conditional deletion, TEAD inhibition, chromatin immunoprecipitation sequencing, gain/loss-of-function studies Gastroenterology High 35550144
2022 YAP1 regulates gastruloid fate patterning by attenuating Nodal signaling. YAP1 knockout gastruloids show reduced ectoderm and enlarged mesoderm/endoderm. YAP1 directly represses chromatin accessibility and transcription of NODAL and FOXH1 genes, preventing hyperactive SMAD2/3 nuclear retention and thereby enabling ectoderm differentiation. YAP1 knockout hESC gastruloids, epigenome (ATAC-seq) and transcriptome (RNA-seq) analysis, immunostaining for SMAD2/3 localization Stem cell reports High 35063126
2022 Small-molecule cyanamide compounds form a covalent bond with a conserved cysteine in the TEAD palmitate-binding cavity, inhibiting YAP1 binding to TEADs with submicromolar IC50 values. Co-crystal structures with TEAD2 enabled structure-activity relationship studies. Inhibition suppressed CTGF mRNA and TEAD1-4 transcriptional activity in mammalian cells. Covalent inhibitor synthesis, co-crystal structures with TEAD2, time/concentration-dependent kinetics (kinact/KI), cellular reporter assays (CTGF mRNA, TEAD transcriptional activity), YAP1-TEAD binding inhibition assay Journal of medicinal chemistry High 36562717
2022 CIC (Capicua) directly represses YAP1 transcription by binding non-consensus GGAAGGAA DNA-binding motifs in a proximal YAP1 regulatory element in an ERK-regulated manner. Silencing YAP1 in CIC-deficient cells restores MAPK inhibitor sensitivity and suppresses tumor growth. ChIP, reporter assays with GGAA motif mutations, siRNA knockdown epistasis, tumor growth assays Cell reports Medium 36198276
2022 YAP1 and PRDM14 individually activate transcription of CALM2 and SLC2A1 (GLUT1) as key downstream targets. PRDM14 can rescue cell proliferation and tumorigenesis upon YAP1 suppression. CALM2 or SLC2A1 expression is required for this rescue, placing them as essential mediators of oncogenic YAP1 signaling. Genome-scale genetic rescue screen (inducible YAP1 shRNA), xenograft models, colon cancer organoids, transcriptional analysis Developmental cell Medium 34990589
2022 YAP1 activity alone (in a Hippo-pathway mutated background) is sufficient to maintain established mesothelioma tumor growth in vivo. Conditional YAP1 downregulation in established xenografts leads to inhibition of YAP1/TEAD-dependent gene transcription and tumor regression, but only in YAP1-activated Hippo-mutant background, not in Hippo-independent cancer cells. Conditional YAP1 knockdown in xenografts, in vitro apoptosis assays, in vivo tumor regression studies, gene expression analysis BMC cancer Medium 35689194
2023 ATXN3 (deubiquitinase) interacts with the WW domains of YAP1 and protects YAP1 from ubiquitination-mediated degradation, promoting tumor growth. CRISPR-Cas9 deletion of ATXN3 decreases YAP1 protein without altering its mRNA. YAP1 reconstitution rescues the growth inhibition caused by ATXN3 suppression. CRISPR-Cas9 gene deletion, co-immunoprecipitation, ubiquitination assays, YAP1 rescue overexpression, immunohistology American journal of cancer research Medium 37818078
2023 OTUD7B deubiquitinase deubiquitinates and stabilizes YAP1 protein, enhancing YAP1 activity and upregulating NUAK2 (and other YAP1 targets including Snail, Slug, CDK6, CTGF, BIRC5) to accelerate gastric cancer progression. Co-immunoprecipitation, ubiquitination assays, OTUD7B overexpression/knockdown, in vitro and in vivo tumor assays Digestive and liver disease Medium 37429790
2023 ENO1, acting as an RNA-binding protein, binds CUG-rich elements in YAP1 mRNA to promote its translation. ENO1 and YAP1 cooperatively regulate arachidonic acid metabolism via inverse regulation of PLCB1 and HPGD, with subsequent PGE2 accumulation driving cancer progression. RNA-binding protein assay, mRNA translation assays, gene knockdown, metabolic profiling, in vivo tumor models Nature chemical biology Medium 37500770
2023 YAP1 inhibits progesterone receptor (PGR) expression through upregulation of miR-21-5p. YAP1 binding to the miR-21 promoter region was confirmed by ChIP-PCR; miR-21-5p in turn reduces PGR mRNA via RNA immunoprecipitation-validated interaction. Knockdown of YAP1 or verteporfin treatment reduces miR-21-5p, increases PGR expression, and enhances decidualization. ChIP-PCR, RNA immunoprecipitation, YAP1 inhibitor (verteporfin), siRNA knockdown, mouse endometriosis model Human reproduction Medium 37071897
2024 TRAF6 stabilizes YAP1 protein through K63-linked polyubiquitination, which promotes formation of a YAP1/TFCP2 transcriptional complex that drives PD-L1 transcription in melanoma cells. TRAF6 suppression downregulates PD-L1 membrane expression. CRISPR interference screening, in vitro and in vivo assays, co-immunoprecipitation, ubiquitination assays (K63-linkage specific) Cancer letters Medium 38583649
2024 CBX4 (SUMO E3 ligase) induces SUMO1 modification of YAP1 at K97 and K280, which competitively inhibits YAP1 S127 phosphorylation (inhibitory Hippo phosphorylation), thereby preserving YAP1 stability and promoting its cytoplasm-nuclear transport and anti-senescence activity in gastric cancer. Co-immunoprecipitation, SUMOylation site mutagenesis (K97, K280), phosphorylation assays (S127), ChIP, high-throughput sequencing Drug resistance updates Medium 39154499
2024 NEK1 kinase phosphorylates YAP1 at Y407 via an AR→TLK1B→NEK1→YAP1-Y407 sequential kinase cascade. YAP1-Y407F dominant mutant reprograms the YAP1 transcriptome, reduces TEAD- and p73-regulated gene expression, and mediates sensitivity to MMC. YAP1 overexpression (but not Y407F) transforms LNCaP cells to androgen-independent growth. Phospho-site mutagenesis (Y407F), transcriptome reprogramming analysis, dominant expression assays, NEK1 haploinsufficient TRAMP mice, immunohistochemistry Biomedicines Medium 36979713
2024 Stromal softness promotes YAP1 degradation via an autophagic-lysosomal pathway (not Hippo/proteasome). In soft extracellular matrix, PTEN is upregulated and promotes lysosomal biogenesis, activating cathepsins that directly degrade YAP1. Purified cathepsin L can directly digest YAP1 under acidic conditions in vitro. In vitro reconstitution (purified cathepsin L + YAP1), hydrogel stiffness matrices, lysosomal inhibition (chloroquine), PTEN manipulation, in vivo liver fibrosis models Cellular and molecular life sciences High 39460766
2024 DAPAGLIFLOZIN (SGLT2 inhibitor) suppresses gastric cancer by decreasing OTUD5 expression, which increases YAP1 ubiquitination and degradation. Overexpression of OTUD5 in gastric cancer cells partly reverses the anti-tumor effect of dapagliflozin, establishing OTUD5 as a deubiquitinase that stabilizes YAP1. OTUD5 overexpression rescue, ubiquitination assays, in vitro and in vivo tumor models, drug treatment European journal of pharmacology Medium 39293571
2019 Endothelial YAP1 regulates Tie2 (angiogenic factor receptor) expression; knockdown of YAP1 in endothelial cells decreases Tie2 expression and inhibits EC sprouting, epithelial cell budding, vascular morphogenesis, and compensatory lung growth after pneumonectomy. siRNA knockdown in endothelial cells, in vitro sprouting assay, in vivo gel implantation on mouse lung, pneumonectomy model, Tie2 expression analysis American journal of respiratory cell and molecular biology Medium 30156429
2016 MST1 activation by shikonin inhibits GLUT1 and C-MYC expression via the MST1-YAP1-TEAD1 axis in human leukemia cells. RNAi experiments confirmed this regulatory axis. YAP1 positively regulates C-MYC mRNA in complex with TEAD1, while it negatively regulates C-MYC levels in cooperation with MST1. Depletion of TEAD1 inhibits lactate production. RNAi knockdown of pathway components, pharmacological MST1 activation, TEAD1 ChIP binding site analysis, lactate production assay Experimental cell research Medium 27793648
2020 METTL14-mediated m6A modification of YAP1 mRNA promotes YTHDF2-mediated transcript decay, reducing YAP1 expression and stemness in TNBC. Loss of METTL14 (driven by LSD1-mediated H3K4 demethylation) blocks m6A on YAP1 mRNA, preventing YTHDF2-dependent decay and sustaining YAP1 protein levels and Hippo-independent YAP1 signaling. m6A-IP sequencing, RNA-IP, ChIP, luciferase reporter assays, KO/KD experiments, tissue microarray validation Journal of experimental & clinical cancer research Medium 39563370

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 TEAD/TEF transcription factors utilize the activation domain of YAP65, a Src/Yes-associated protein localized in the cytoplasm. Genes & development 608 11358867
2020 SCLC Subtypes Defined by ASCL1, NEUROD1, POU2F3, and YAP1: A Comprehensive Immunohistochemical and Histopathologic Characterization. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 431 33011388
1994 Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product. Oncogene 373 8035999
2006 Defects in yolk sac vasculogenesis, chorioallantoic fusion, and embryonic axis elongation in mice with targeted disruption of Yap65. Molecular and cellular biology 348 16354681
2019 Recurrent YAP1-MAML2 and YAP1-NUTM1 fusions in poroma and porocarcinoma. The Journal of clinical investigation 201 31145701
2016 PAK proteins and YAP-1 signalling downstream of integrin beta-1 in myofibroblasts promote liver fibrosis. Nature communications 193 27535340
2002 Yes-associated protein (YAP65) interacts with Smad7 and potentiates its inhibitory activity against TGF-beta/Smad signaling. Oncogene 175 12118366
2018 A time for YAP1: Tumorigenesis, immunosuppression and targeted therapy. International journal of cancer 149 29696628
2020 YAP1 Expression in SCLC Defines a Distinct Subtype With T-cell-Inflamed Phenotype. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 140 33248321
2017 Reciprocal expression of INSM1 and YAP1 defines subgroups in small cell lung cancer. Oncotarget 135 29088741
2021 YAP1 and its fusion proteins in cancer initiation, progression and therapeutic resistance. Developmental biology 130 33428889
2019 Timely expression and activation of YAP1 in granulosa cells is essential for ovarian follicle development. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 104 31199671
2022 Activation of YAP1 by N6-Methyladenosine-Modified circCPSF6 Drives Malignancy in Hepatocellular Carcinoma. Cancer research 93 34916222
2016 A ZEB1-miR-375-YAP1 pathway regulates epithelial plasticity in prostate cancer. Oncogene 91 27270433
2017 YAP1 and COX2 Coordinately Regulate Urothelial Cancer Stem-like Cells. Cancer research 89 29180467
2020 YAP1 mediates gastric adenocarcinoma peritoneal metastases that are attenuated by YAP1 inhibition. Gut 88 32345613
2014 The mammalian Hippo pathway: regulation and function of YAP1 and TAZ. Cellular and molecular life sciences : CMLS 86 25266986
2022 NOTCH-YAP1/TEAD-DNMT1 Axis Drives Hepatocyte Reprogramming Into Intrahepatic Cholangiocarcinoma. Gastroenterology 76 35550144
2023 ENO1 promotes liver carcinogenesis through YAP1-dependent arachidonic acid metabolism. Nature chemical biology 71 37500770
2020 Telomere dysfunction activates YAP1 to drive tissue inflammation. Nature communications 66 32958778
2020 Recurrent YAP1 and MAML2 Gene Rearrangements in Retiform and Composite Hemangioendothelioma. The American journal of surgical pathology 62 32991341
2007 The RUNX2 transcription factor cooperates with the YES-associated protein, YAP65, to promote cell transformation. Cancer biology & therapy 59 17438369
2018 IL-6/YAP1/β-catenin signaling is involved in intervertebral disc degeneration. Journal of cellular physiology 58 30511395
2018 Mediator kinase CDK8/CDK19 drives YAP1-dependent BMP4-induced EMT in cancer. Oncogene 54 29780169
2020 Circular RNA YAP1 attenuates osteoporosis through up-regulation of YAP1 and activation of Wnt/β-catenin pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 53 32768931
2018 YAP1 is essential for osteoclastogenesis through a TEADs-dependent mechanism. Bone 51 29432919
2014 The dual functions of YAP-1 to promote and inhibit cell growth in human malignancy. Cancer metastasis reviews 50 24346160
2020 Isorhapontigenin protects against doxorubicin-induced cardiotoxicity via increasing YAP1 expression. Acta pharmaceutica Sinica. B 47 33777675
2018 YAP1-TEAD1 signaling controls angiogenesis and mitochondrial biogenesis through PGC1α. Microvascular research 47 29680477
2019 TEAD4, YAP1 and WWTR1 prevent the premature onset of pluripotency prior to the 16-cell stage. Development (Cambridge, England) 44 31444221
2024 Residual ANTXR1+ myofibroblasts after chemotherapy inhibit anti-tumor immunity via YAP1 signaling pathway. Nature communications 42 38346978
2022 YAP1 activation by human papillomavirus E7 promotes basal cell identity in squamous epithelia. eLife 42 35170430
2020 Utility of YAP1 and NUT immunohistochemistry in the diagnosis of porocarcinoma. Journal of cutaneous pathology 42 33222286
2018 Fatal correlation between YAP1 expression and glioma aggressiveness: clinical and molecular evidence. The Journal of pathology 42 30009411
2022 Both YAP1-MAML2 and constitutively active YAP1 drive the formation of tumors that resemble NF2 mutant meningiomas in mice. Genes & development 41 36008139
2020 AMOTL1 enhances YAP1 stability and promotes YAP1-driven gastric oncogenesis. Oncogene 38 32313226
2020 YAP1/TAZ drives ependymoma-like tumour formation in mice. Nature communications 38 32404936
2019 STUB1 suppresseses tumorigenesis and chemoresistance through antagonizing YAP1 signaling. Cancer science 36 31393050
2019 Amot and Yap1 regulate neuronal dendritic tree complexity and locomotor coordination in mice. PLoS biology 35 31042703
2019 Endothelial YAP1 in Regenerative Lung Growth through the Angiopoietin-Tie2 Pathway. American journal of respiratory cell and molecular biology 34 30156429
2024 CSN6-SPOP-HMGCS1 Axis Promotes Hepatocellular Carcinoma Progression via YAP1 Activation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 33 38308184
2021 Reciprocal YAP1 loss and INSM1 expression in neuroendocrine prostate cancer. The Journal of pathology 30 34431104
2019 Requirement for YAP1 signaling in myxoid liposarcoma. EMBO molecular medicine 30 30898787
2022 YAP1 regulates the self-organized fate patterning of hESC-derived gastruloids. Stem cell reports 29 35063126
2019 Mechanotransduction and Cytoskeleton Remodeling Shaping YAP1 in Gastric Tumorigenesis. International journal of molecular sciences 29 30934860
2024 CBX4 counteracts cellular senescence to desensitize gastric cancer cells to chemotherapy by inducing YAP1 SUMOylation. Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy 27 39154499
2023 YAP1 and WWTR1 expression inversely correlates with neuroendocrine markers in Merkel cell carcinoma. The Journal of clinical investigation 26 36719743
2020 Role of Hippo-YAP1/TAZ pathway and its crosstalk in cardiac biology. International journal of biological sciences 26 32760212
2024 TRAF6 enhances PD-L1 expression through YAP1-TFCP2 signaling in melanoma. Cancer letters 25 38583649
2023 Targeting YAP1 ameliorates progesterone resistance in endometriosis. Human reproduction (Oxford, England) 25 37071897
2016 Shikonin regulates C-MYC and GLUT1 expression through the MST1-YAP1-TEAD1 axis. Experimental cell research 25 27793648
2006 Yes-associated protein (YAP65) in relation to Smad7 expression in human pancreatic ductal adenocarcinoma. International journal of molecular medicine 25 16596258
2023 PLAGL2 promotes bladder cancer progression via RACGAP1/RhoA GTPase/YAP1 signaling. Cell death & disease 23 37454211
2022 Dihydroartemisinin promoted FXR expression independent of YAP1 in hepatocellular carcinoma. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23 35616366
2020 MiR-27b-3p suppresses glioma development via targeting YAP1. Biochemistry and cell biology = Biochimie et biologie cellulaire 22 32567955
2023 Distinct regulations driving YAP1 expression loss in poroma, porocarcinoma and RB1-deficient skin carcinoma. Histopathology 21 36720791
2023 The circular RNA circHelz enhances cardiac fibrosis by facilitating the nuclear translocation of YAP1. Translational research : the journal of laboratory and clinical medicine 21 36775059
2019 BRCA1/BARD1-dependent ubiquitination of NF2 regulates Hippo-YAP1 signaling. Proceedings of the National Academy of Sciences of the United States of America 21 30918126
2022 PAF1 cooperates with YAP1 in metaplastic ducts to promote pancreatic cancer. Cell death & disease 19 36180487
2022 Small-Molecule Cyanamide Pan-TEAD·YAP1 Covalent Antagonists. Journal of medicinal chemistry 19 36562717
2024 YAP1 preserves tubular mitochondrial quality control to mitigate diabetic kidney disease. Redox biology 18 39608245
2019 Interaction of YAP1 and mTOR promotes bladder cancer progression. International journal of oncology 18 31789387
2022 YAP1 and PRDM14 converge to promote cell survival and tumorigenesis. Developmental cell 17 34990589
2022 The role of YAP1 in small cell lung cancer. Human cell 17 35072899
2022 YAP1 is essential for malignant mesothelioma tumor maintenance. BMC cancer 17 35689194
2019 Hepatic YAP1-TFE3 Rearranged Epithelioid Hemangioendothelioma. Case reports in gastrointestinal medicine 17 31341686
2023 Sarsasapogenin inhibits YAP1-dependent chondrocyte ferroptosis to alleviate osteoarthritis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 16 37879209
2022 Role of YAP1 Signaling in Biliary Development, Repair, and Disease. Seminars in liver disease 16 35073587
2020 LncRNA-ROR/microRNA-185-3p/YAP1 axis exerts function in biological characteristics of osteosarcoma cells. Genomics 16 32898639
2024 Combined BET and MEK Inhibition synergistically suppresses melanoma by targeting YAP1. Theranostics 15 38169595
2024 YAP1 Status Defines Two Intrinsic Subtypes of LCNEC with Distinct Molecular Features and Therapeutic Vulnerabilities. Clinical cancer research : an official journal of the American Association for Cancer Research 15 39150543
2024 METTL14 suppresses the expression of YAP1 and the stemness of triple-negative breast cancer. Journal of experimental & clinical cancer research : CR 15 39563370
2023 FAP promotes metastasis and chemoresistance via regulating YAP1 and macrophages in mucinous colorectal adenocarcinoma. iScience 15 37213233
2025 YAP1 facilitates the pathogenesis of psoriasis via modulating keratinocyte proliferation and inflammation. Cell death & disease 14 40108109
2024 FOXP4 Is a Direct YAP1 Target That Promotes Gastric Cancer Stemness and Drives Metastasis. Cancer research 14 39047223
2022 Capicua suppresses YAP1 to limit tumorigenesis and maintain drug sensitivity in human cancer. Cell reports 14 36198276
2021 An optogenetic method for interrogating YAP1 and TAZ nuclear-cytoplasmic shuttling. Journal of cell science 14 34060624
2021 Clinical significance of YAP1 and TAZ in esophageal squamous cell carcinoma. Medicine 14 34260541
2020 Circular RNA Gprc5a Promotes HCC Progression by Activating YAP1/TEAD1 Signalling Pathway by Sponging miR-1283. OncoTargets and therapy 14 32547082
2023 YAP1 is essential for self-organized differentiation of pluripotent stem cells. Biomaterials advances 13 36774716
2023 ATXN3 deubiquitinates YAP1 to promote tumor growth. American journal of cancer research 13 37818078
2020 Heterozygous Loss of Yap1 in Mice Causes Progressive Cataracts. Investigative ophthalmology & visual science 13 33085740
2024 Yap1 alleviates sepsis associated encephalopathy by inhibiting hippocampus ferroptosis via maintaining mitochondrial dynamic homeostasis. Journal of cellular and molecular medicine 12 39400418
2023 OTUD7B deubiquitinates and stabilizes YAP1 to upregulate NUAK2 expression, thus accelerating gastric cancer procession. Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 12 37429790
2022 Wnt signaling promotes tooth germ development through YAP1-TGF-β signaling. Biochemical and biophysical research communications 12 36150241
2021 Dynamic patterns of YAP1 expression and cellular localization in the developing and injured utricle. Scientific reports 12 33495483
2021 YAP1-mediated regulation of mitochondrial dynamics in IDH1 mutant gliomas. Journal of cell science 12 34651186
2018 Yap1/Taz are essential for the liver development in zebrafish. Biochemical and biophysical research communications 12 29859190
2024 N6-methyladenosine-modified circTEAD1 stabilizes Yap1 mRNA to promote chordoma tumorigenesis. Clinical and translational medicine 11 38659080
2024 HPV18 E7 inhibits LATS1 kinase and activates YAP1 by degrading PTPN14. mBio 11 39248565
2024 Dapagliflozin suppressed gastric cancer growth via regulating OTUD5 mediated YAP1 deubiquitination. European journal of pharmacology 11 39293571
2023 NEK1-Mediated Phosphorylation of YAP1 Is Key to Prostate Cancer Progression. Biomedicines 11 36979713
2025 Curcumin targets YAP1 to enhance mitochondrial function and autophagy, protecting against UVB-induced photodamage. Frontiers in immunology 10 40201180
2025 CAFs activated by YAP1 upregulate cancer matrix stiffness to mediate hepatocellular carcinoma progression. Journal of translational medicine 10 40241143
2024 CNS tumors with PLAGL1-fusion: beyond ZFTA and YAP1 in the genetic spectrum of supratentorial ependymomas. Acta neuropathologica communications 10 38581034
2024 Stromal softness confines pancreatic cancer growth through lysosomal-cathepsin mediated YAP1 degradation. Cellular and molecular life sciences : CMLS 10 39460766
2023 Dihydroartemisinin inhibited interleukin-18 expression by decreasing YAP1 in hepatocellular carcinoma cells. Acta histochemica 10 37119608
2023 MUC13 drives cancer aggressiveness and metastasis through the YAP1-dependent pathway. Life science alliance 10 37793774
2021 Ibrutinib Blocks YAP1 Activation and Reverses BRAF Inhibitor Resistance in Melanoma Cells. Molecular pharmacology 10 34732527
2019 HNF4α and CDX2 Regulate Intestinal YAP1 Promoter Activity. International journal of molecular sciences 10 31216773

Missed literature

Know a paper Affinage missed for YAP1? Flag it for the maintainers and the community.

No submissions yet.