Affinage

LATS1

Serine/threonine-protein kinase LATS1 · UniProt O95835

Length
1130 aa
Mass
126.9 kDa
Annotated
2026-06-10
100 papers in source corpus 31 papers cited in narrative 31 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

LATS1 is a Ser/Thr kinase that serves as the central effector of the Hippo tumor-suppressor pathway, a module first defined genetically in Drosophila where Warts (LATS) acts downstream of Hippo and Salvador to restrain proliferation and promote apoptosis (PMID:14502294). In its canonical role, LATS1 directly binds and phosphorylates YAP, sequestering this oncoprotein in the cytoplasm and inactivating its transcriptional output (PMID:18158288). LATS1 is itself switched on by upstream kinases: MST2 phosphorylates the activation-loop site S909 and the hydrophobic-motif site T1079 (PMID:15688006), a step organized by WWC proteins and SAV1 that recruit MST1/2 to LATS (PMID:35429439), with additional MST-independent activators including the Kibra–PTPN14 axis (PMID:25023289) and MAP4K4 (PMID:25453828); PARD3-directed PP1A dephosphorylation provides an off-switch (PMID:26116754). Beyond YAP, LATS1 phosphorylates a diverse substrate set linking it to genome integrity and immunity: MYPT1-Ser445 to antagonize PLK1 at the G2 DNA-damage checkpoint (PMID:22641346), MTF1 to attenuate heavy-metal responses in a zinc-gated feedback loop (PMID:35027733), STAT1-Ser727 to drive IRF1/NLRC5-dependent MHC-I expression (PMID:38383447), FOXL2 to control granulosa-cell differentiation (PMID:20407010), and CHO1 to govern cytokinesis through LIMK1 (PMID:25786116). LATS1 also exerts YAP/TAZ-independent functions, including kinase-independent scaffolding that stabilizes Beclin-1 via K27-linked ubiquitination to suppress autophagy (PMID:31848340) and signal transduction downstream of the type I interferon receptor IFNAR2 via Tyk2-mediated tyrosine phosphorylation (PMID:35394840). LATS1 abundance is tightly set by numerous E3 ubiquitin ligases that drive its proteasomal degradation—SPOP/Cullin3 (PMID:32460168), NEDD4 recruited by PMEPA1a (PMID:31605013), HERC4 (PMID:30710319), WWP2 (PMID:36803368), and ITCH recruited upon Gα13 activation (PMID:31569999)—as well as by CBP-mediated acetylation at K751 (PMID:33945069) and METTL3/YTHDF2-dependent m6A destabilization of its mRNA (PMID:36609396).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2003 High

    Established the genetic architecture placing LATS/Warts within a defined kinase module, answering how an upstream growth-control signal is relayed to proliferation and apoptosis decisions.

    Evidence Genetic epistasis and co-immunoprecipitation in Drosophila mutants

    PMID:14502294

    Open questions at the time
    • Did not identify the LATS substrate executing growth control
    • Mammalian relevance not yet demonstrated
  2. 2002 High

    Showed that LATS1 catalytic activity drives cell-cycle arrest and apoptosis, defining it functionally as a tumor suppressor rather than a passive scaffold.

    Evidence Adenoviral overexpression with kinase-dead mutant, cell-cycle and xenograft assays in cancer cells

    PMID:11850843

    Open questions at the time
    • Direct kinase substrate for these effects not identified
    • CDC2 association mechanism not resolved
  3. 2005 High

    Defined the upstream activation mechanism by identifying the two regulatory phosphosites through which MST2 turns LATS1 on.

    Evidence In vitro kinase assay with mass-spectrometry mapping of S909 and T1079, deletion analysis

    PMID:15688006

    Open questions at the time
    • Scaffolding requirements for the MST2-LATS1 reaction not addressed
    • Did not link activation to a downstream output
  4. 2005 High

    Linked LATS1 to mitotic exit via MOB1A, connecting the kinase to control of cell division timing.

    Evidence Reciprocal co-IP plus siRNA and overexpression with microtubule poisons and live-cell analysis

    PMID:16061636

    Open questions at the time
    • Molecular mechanism of MOB1A-dependent mitotic exit unresolved
    • No substrate identified for this function
  5. 2007 High

    Identified the central canonical substrate, showing LATS1 directly phosphorylates YAP to drive its cytoplasmic sequestration and a substrate consensus motif.

    Evidence In vitro kinase assay, co-IP, subcellular fractionation and microarray

    PMID:18158288

    Open questions at the time
    • Did not enumerate non-YAP substrates
    • Physiological contexts of YAP control not delineated
  6. 2010 Medium

    Extended the LATS1 substrate repertoire to transcription-factor control, phosphorylating FOXL2 in granulosa-cell differentiation.

    Evidence Yeast two-hybrid, co-IP, in vitro kinase assay and promoter reporter with kinase-dead controls in mouse ovary context

    PMID:20407010

    Open questions at the time
    • Phosphosite on FOXL2 not precisely mapped
    • In vivo gonadal requirement not genetically tested
  7. 2012 High

    Connected LATS1 to the DNA-damage checkpoint by identifying MYPT1-Ser445 phosphorylation as the means to antagonize PLK1.

    Evidence Phosphoproteomics, in vitro kinase assay, phospho-specific antibodies and LATS1-knockout fibroblasts

    PMID:22641346

    Open questions at the time
    • Integration with canonical Hippo signaling not addressed
    • Upstream activation of LATS1 in this context unclear
  8. 2014 Medium

    Revealed MST-independent LATS1 activation, with Kibra-PTPN14 and MAP4K4 each able to engage and activate the kinase.

    Evidence Co-IP, domain mapping, LATS1 kinase assays and Drosophila/mammalian epistasis

    PMID:25023289 PMID:25453828

    Open questions at the time
    • Relative contribution versus MST pathway in vivo unquantified
    • How these inputs converge on the activation loop not resolved
  9. 2015 Medium

    Defined inhibitory and localization controls of LATS1 activity, including PARD3-PP1A dephosphorylation and junctional activation sites, plus new mitotic substrates and stability targets.

    Evidence Co-IP, phosphatase and kinase assays, phospho-specific antisera and live imaging across mammalian and Drosophila systems

    PMID:25786116 PMID:26116754 PMID:26420589 PMID:26530630

    Open questions at the time
    • Spatial coordination of activation versus inactivation not unified
    • Cdc25B regulation occurs without direct phosphorylation, mechanism incomplete
  10. 2016 High

    Demonstrated that LATS1/2 loss reshapes anti-tumor immunity through nucleic-acid-rich extracellular vesicles, expanding LATS function beyond cell-autonomous growth control.

    Evidence Syngeneic mouse tumor models with genetic deletion, EV characterization and immune-depletion experiments

    PMID:27912060

    Open questions at the time
    • Kinase-substrate basis of EV phenotype not defined
    • Whether effect depends on LATS catalytic activity unaddressed
  11. 2017 High

    Uncovered a YAP/TAZ-independent role: LATS-dependent ERα degradation, broadening the non-canonical reach of the pathway.

    Evidence shRNA screen in primary breast epithelial cells, co-IP, ubiquitination and proteasome-inhibition assays identifying DCAF1

    PMID:28068668

    Open questions at the time
    • Direct enzymatic role of LATS in this degradation not defined
    • Generalizability beyond breast cells untested
  12. 2019 High

    Defined a kinase-independent scaffolding function of LATS1, stabilizing Beclin-1 by K27-linked ubiquitination to suppress autophagy.

    Evidence Knockout/knockdown, in vitro ubiquitination with site mutagenesis and kinase-dead controls in hepatocellular carcinoma cells

    PMID:31848340

    Open questions at the time
    • The ubiquitin ligase recruited by LATS1 not identified
    • Distinction from LATS2 mechanistically unexplained
  13. 2019 Medium

    Established LATS1 protein abundance as a heavily regulated node, with multiple E3 ligases and degron-dependent inputs controlling its half-life.

    Evidence Co-IP, ubiquitination and cycloheximide-chase assays defining HERC4, PMEPA1a-NEDD4, and Gα13-recruited ITCH

    PMID:30710319 PMID:31569999 PMID:31605013

    Open questions at the time
    • Hierarchy and context-specificity among ligases unresolved
    • Endogenous physiological triggers not fully defined
  14. 2020 Medium

    Showed downstream consequences of LATS1/2 loss in tissue, including TEAD-independent YAP/TAZ-TLE inhibition of Wnt signaling and SPOP/Cullin3-mediated LATS1 turnover.

    Evidence Conditional knockout mice, TEAD-inhibitor and proteomics; co-IP and stability assays in kidney cancer cells

    PMID:32259481 PMID:32460168

    Open questions at the time
    • Tissue specificity of these effects not generalized
    • Crosstalk with canonical TEAD output not quantified
  15. 2021 Medium

    Identified post-translational and biophysical tuning of LATS1, with K751 acetylation balancing stability against activity and lncRNA-driven phase separation suppressing YAP phosphorylation.

    Evidence Acetyltransferase and phase-separation assays, site mutagenesis, ubiquitination and YAP-phosphorylation readouts

    PMID:33945069 PMID:34267352

    Open questions at the time
    • Physiological stimuli driving acetylation/phase separation unclear
    • Single-lab findings for each mechanism
  16. 2022 Medium

    Expanded LATS1 into innate immunity and stress sensing, signaling downstream of IFNAR2 via Tyk2 and gating MHC-I and heavy-metal responses through STAT1-Ser727 and MTF1.

    Evidence Co-IP, sequential phosphorylation cascades, in vitro kinase assays, zinc-binding assays and knockout cells with in vivo confirmation

    PMID:35027733 PMID:35394840 PMID:35429439 PMID:38383447

    Open questions at the time
    • Tyrosine-phosphorylation step is non-canonical and mechanistically distinct from Ser/Thr activation
    • Integration of these branches with Hippo signaling not unified
  17. 2023 Medium

    Added mRNA-level and ligase-level control of LATS1, via METTL3/YTHDF2 m6A destabilization and WWP2-mediated degradation, each activating YAP.

    Evidence MeRIP-seq, RIP-qPCR, RNA-stability analysis; co-IP and in vivo ubiquitination assays

    PMID:36609396 PMID:36803368

    Open questions at the time
    • Conditions selecting mRNA versus protein control not defined
    • Single-lab studies
  18. 2024 Medium

    Showed viral subversion of LATS1 activation, with HPV18 E7 degrading PTPN14 to lower LATS1 T1079 phosphorylation and de-repress YAP.

    Evidence PTPN14 knockout, phospho-specific antibodies, PPxY-motif mutagenesis and keratinocyte differentiation assays

    PMID:39248565

    Open questions at the time
    • MST-independence versus dependence in keratinocytes only partially resolved
    • Single-lab finding

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LATS1's many non-canonical branches—autophagy scaffolding, interferon and metal-stress signaling, immune-vesicle output—are coordinated with its canonical YAP-suppressing kinase activity within a single cell remains unresolved.
  • No unified model linking kinase-dependent and kinase-independent functions
  • Context determinants selecting among substrates unknown
  • Structural basis of differential substrate recognition uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 7 GO:0016740 transferase activity 4 GO:0098772 molecular function regulator activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 2 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-392499 Metabolism of proteins 5 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 4 R-HSA-168256 Immune System 3 R-HSA-9612973 Autophagy 1
Partners
IFNAR2MAP4K4MOB1AMST2PTPN14SAV1WWC1YAP1

Evidence

Reading pass · 31 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2007 LATS1 directly binds to and phosphorylates YAP (Yes-associated protein) in vitro and in vivo, and inactivates YAP oncogenic function by sequestering YAP in the cytoplasm after phosphorylation. The consensus phosphorylation sequence for LATS/Ndr kinase substrates was identified as HX(R/H/K)XX(S/T). In vitro kinase assay, co-immunoprecipitation, subcellular fractionation, microarray analysis The Journal of biological chemistry High 18158288
2005 Human Mst2 (Ste20-like kinase, MST2) phosphorylates and activates LATS1 at two conserved regulatory sites: S909 in the activation loop and T1079 within the hydrophobic motif, identified by mass spectrometry. Regulation occurs through the C-terminal catalytic domain of LATS1. In vitro kinase assay, deletion analysis, mass spectrometry, co-immunoprecipitation Oncogene High 15688006
2003 In Drosophila, Hippo (Hpo) acts together with Salvador (Sav) and Warts (Wts/LATS) in a signaling module. Sav binds to a regulatory domain of Hpo essential for its function, placing Wts/LATS downstream in this pathway that coordinately regulates cell proliferation (via Cyclin E) and apoptosis (via DIAP1 and hid). Genetic epistasis, co-immunoprecipitation, Drosophila mutant analysis Nature cell biology High 14502294
2005 LATS1 interacts with MOB1A (a protein whose yeast homologue associates with mitotic exit network kinases). Moderate overexpression of LATS1 in cells exposed to microtubule poisons facilitated mitotic exit in a MOB1A-dependent manner; siRNA-mediated suppression of LATS1 or MOB1A prolonged telophase. Co-immunoprecipitation, siRNA knockdown, overexpression in cells with microtubule poisons, live cell analysis Cancer research High 16061636
2002 LATS1 associates with CDC2 in early mitosis and its ectopic expression in cancer cells down-regulates Cyclin A and Cyclin B protein levels, reduces CDC2 kinase activity, causes G2/M blockade, up-regulates BAX, and induces apoptosis. LATS1 kinase activity is required for these effects. Adenoviral overexpression, cell cycle analysis, kinase activity assay, western blot, soft agar/xenograft assay Oncogene High 11850843
2012 LATS1 phosphorylates MYPT1 (myosin phosphatase-targeting subunit 1) at serine 445. This phosphorylation enables MYPT1 to dephosphorylate PLK1 Thr210, thereby antagonizing PLK1 activity. LATS1 depletion increased PLK1 activity and reduced G2 DNA-damage checkpoint arrest. Phosphoproteomic screening, in vitro kinase assay, phospho-specific antibodies, siRNA knockdown, LATS1 knockout mouse fibroblasts The Journal of cell biology High 22641346
2022 WWC proteins (WWC1/2/3) directly interact with both LATS1/2 and SAV1; SAV1 in turn recruits MST1/2 to phosphorylate and activate LATS1/2. WWC proteins thus act as organizers in a signaling module mediating LATS1/2 activation by MST1/2, and a minimum interaction interface on WWC sufficient to activate LATS1/2 was defined. Co-immunoprecipitation, in vitro kinase assay, structure-function analysis (minigene), tumor xenograft model Molecular cell High 35429439
2014 PTPN14 interacts with Kibra protein (via PTPN14 PPXY domain and Kibra WW domain) and both independently and cooperatively activate LATS1, leading to cytoplasmic sequestration of YAP. PTPN14 also increases LATS1 protein stability. LATS1 activation by PTPN14 is independent of MST kinases. Co-immunoprecipitation, domain mapping, LATS1 kinase assay, siRNA knockdown, 3D morphogenesis assay The Journal of biological chemistry Medium 25023289
2015 PARD3 promotes interaction between PP1A phosphatase and LATS1, leading to LATS1 dephosphorylation and inactivation, thereby causing dephosphorylation and activation of TAZ. The cytoplasmic (but not tight-junction-associated) form of PARD3 mediates this regulation. Co-immunoprecipitation, phosphorylation assay, domain analysis, siRNA knockdown, reporter assay EMBO reports Medium 26116754
2010 LATS1 phosphorylates FOXL2 (Forkhead L2) at a serine residue, enhances FOXL2's activity as a transcriptional repressor of the StAR promoter (a marker of granulosa cell differentiation). This effect requires LATS1 kinase activity. LATS1 and FOXL2 are co-expressed in developing mouse gonads and granulosa cells. Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay, promoter reporter assay, immunohistochemistry in mouse ovary American journal of physiology. Endocrinology and metabolism Medium 20407010
2016 Loss of LATS1/2 in tumor cells causes secretion of nucleic-acid-rich extracellular vesicles that induce a type I interferon response via the Toll-like receptors–MYD88/TRIF pathway, enhancing anti-tumor immune responses and causing tumor regression dependent on adaptive immunity. Syngeneic mouse tumor models (B16, SCC7, 4T1), LATS1/2 genetic deletion, extracellular vesicle characterization, immune cell depletion experiments Cell High 27912060
2017 In the presence of LATS1/2, estrogen receptor-α (ERα) is targeted for ubiquitination and DCAF1-dependent proteasomal degradation. Absence of LATS1/2 stabilizes ERα together with YAP and TAZ, which together control breast cell fate. This represents a non-canonical (YAP/TAZ-independent) role of LATS. shRNA screen in primary human breast epithelial cells, co-immunoprecipitation, ubiquitination assay, proteasome inhibition experiments Nature High 28068668
2019 LATS1, but not LATS2, represses autophagy in hepatocellular carcinoma cells through a kinase-independent scaffolding mechanism: LATS1 stabilizes Beclin-1 by promoting K27-linked ubiquitination at lysine residues K32 and K263, and this ubiquitination promotes inactive Beclin-1 dimer formation, negatively regulating autophagy. LATS1 knockout/knockdown, in vitro ubiquitination assay, site-directed mutagenesis of Beclin-1 ubiquitination sites, co-immunoprecipitation, kinase-dead mutant Nature communications High 31848340
2022 LATS1/2 phosphorylate and inhibit MTF1, an essential transcription factor for heavy metal response gene transcription, thereby attenuating cellular responses to heavy metals. Accumulated zinc directly binds and inhibits LATS kinase activity, creating a feedback loop. This function is independent of canonical YAP/TAZ effectors. In vitro kinase assay, Hippo pathway knockout cells, transcriptome analysis, zinc-binding assay, reporter assays Nature cell biology High 35027733
2022 LATS1 constitutively binds the type I interferon receptor IFNAR2 and is rapidly tyrosine-phosphorylated by Tyk2 upon IFN-I engagement. Tyrosine-phosphorylated/activated LATS1 translocates to the nucleus and induces CDK8-Ser62 phosphorylation, which in turn phosphorylates STAT1 at Ser727 to achieve full IFN-I antiviral activity. Co-immunoprecipitation (LATS1-IFNAR2), phosphorylation assays (Tyk2→LATS1, LATS1→CDK8, CDK8→STAT1), LATS1 knockout cells, in vivo antiviral experiments Science advances Medium 35394840
2022 LATS1/2 directly interact with and phosphorylate STAT1 at Ser727, promoting STAT1 nuclear accumulation and transcriptional activation of IRF1/NLRC5, which in turn upregulates MHC-I expression. Loss of LATS1/2 reduces MHC-I expression and promotes immune evasion independently of the Hippo-YAP pathway. Co-immunoprecipitation, GST pull-down, in vitro kinase assay (mass spectrometry), ChIP-qPCR, CRISPR-Cas9 knockout, flow cytometry Journal of experimental & clinical cancer research : CR High 38383447
2020 SPOP (an E3 ubiquitin ligase adaptor) specifically interacts with LATS1 and promotes its poly-ubiquitination and proteasomal degradation in a degron-dependent manner via Cullin3. Depletion of Cullin3 upregulates LATS1 protein abundance by prolonging its half-life. Co-immunoprecipitation, ubiquitination assay, cycloheximide chase, Cullin3 knockdown, overexpression/knockdown in kidney cancer cells EBioMedicine Medium 32460168
2019 PMEPA1 isoform a (PMEPA1a) associates with LATS1 and promotes proteasomal degradation of LATS1 by recruiting the E3 ubiquitin ligase NEDD4. Alanine substitution in PMEPA1a at PY motifs abolishes LATS1 degradation. This leads to silencing of Hippo signaling and promotes glioma growth. Co-immunoprecipitation, site-directed mutagenesis (PY motifs), ubiquitination assay, xenograft model, shRNA knockdown Oncogene Medium 31605013
2019 E3 ligase HERC4 ubiquitinates LATS1 and promotes its proteasomal degradation. miRNA-136-5p and miRNA-1285-5p suppress HERC4 expression, thus indirectly stabilizing LATS1. Co-immunoprecipitation, ubiquitination assay, gain/loss-of-function experiments, in vivo tumor assay Protein & cell Medium 30710319
2023 WWP2 (WW domain-containing E3 ubiquitin ligase 2) interacts with LATS1 and promotes its ubiquitination and subsequent proteasomal degradation, leading to increased YAP1 transcriptional activity. Co-immunoprecipitation, immunofluorescence, cycloheximide chase, in vivo ubiquitination assay, xenograft model Cell communication and signaling : CCS Medium 36803368
2021 LATS1 is acetylated by acetyltransferase CBP at K751 and deacetylated by SIRT3 and SIRT4. Acetylation at K751 stabilizes LATS1 (by reducing ubiquitination) but inhibits its kinase activation (by reducing phosphorylation), resulting in reduced YAP phosphorylation and increased YAP nuclear translocation. K751Q (acetylation mimic) promotes lung cancer cell migration/invasion; K751R (acetylation-deficient) inhibits these functions. Site-directed mutagenesis, in vitro acetyltransferase assay, co-immunoprecipitation, ubiquitination assay, phosphorylation assay, functional cancer cell assays Science China. Life sciences Medium 33945069
2015 In Drosophila wing imaginal discs, Warts (LATS) is organized into distinct junctional complexes separate from Hippo, Salvador, and Expanded. Upon Hippo pathway activation, Warts shifts from associating with its inhibitor Jub to its activator Expanded, and Hippo concentrates at Salvador sites. Warts activation occurs specifically at apical junctions where Expanded, Salvador, Hippo, and Warts overlap, as shown by phospho-specific antisera. Live imaging, phospho-specific antisera, genetic manipulation (Drosophila), fractionation/localization analysis Nature communications High 26420589
2014 MAP4K4 (mammalian homolog of Drosophila Misshapen) interacts with LATS1 (Warts homolog) and promotes inhibition of YAP (Yorkie homolog) in mammalian cells, acting as an MST1/2-independent activator of LATS. Co-immunoprecipitation, epistasis analysis in Drosophila and mammalian cells, YAP phosphorylation assay Developmental cell Medium 25453828
2015 LATS1 physically interacts with and regulates the stability of Cdc25B phosphatase. Loss of LATS1 causes abnormal accumulation of Cdc25B protein and hyperactivation of Cdk2 toward nucleophosmin (NPM/B23), suppressing centrosome overduplication. LATS1 does not directly phosphorylate Cdc25B. Co-immunoprecipitation, Lats1 knockout MEFs, centrosome duplication assay, Cdk2 kinase assay, western blot Scientific reports Medium 26530630
2015 LATS1/2 phosphorylate CHO1 at Ser716 in its F-actin-interacting region (absent in MKLP1 splice variant). Phosphorylated CHO1 localizes to centrosomes and midbody, and recruits LIMK1 as binding partner. Overexpression of constitutively phosphorylated or non-phosphorylated CHO1 alters LIMK1 mitotic localization/activation at centrosomes, inhibiting cytokinesis through excessive Cofilin phosphorylation and mislocalization of Ect2. In vitro kinase assay, phospho-specific localization, co-immunoprecipitation (LIMK1-CHO1), overexpression of phospho-mutants in HeLa cells Cell cycle (Georgetown, Tex.) Medium 25786116
2021 lncRNA SNHG9 and its associated phosphatidic acids interact with the C-terminal domain of LATS1, promoting LATS1 liquid-liquid phase separation (LLPS). LATS1 phase separation inhibits LATS1-mediated YAP phosphorylation. RNA pull-down, co-immunoprecipitation, in vitro phase separation assay, YAP phosphorylation assay, domain mapping Cell research Medium 34267352
2019 Gα13 activation induces phosphorylation of LATS1 at serine 909 (activation loop), which recruits ITCH E3 ubiquitin ligase to trigger LATS1 proteasomal degradation, thereby promoting EMT in ovarian cancer. Chimeric G-protein/mutant GPCR synthetic biology, co-immunoprecipitation, ubiquitination assay, phospho-LATS1 S909 western blot FASEB journal Medium 31569999
2023 METTL3 methylates LATS1 mRNA at m6A sites; YTHDF2 recognizes these m6A modifications and reduces LATS1 mRNA stability, thereby decreasing LATS1 protein levels and activating YAP/TAZ in the Hippo pathway. MeRIP-seq, RNA pull-down assay, RIP-qPCR, RNA stability analysis, METTL3/YTHDF2 knockout Journal of experimental & clinical cancer research : CR Medium 36609396
2024 HPV18 E7 degrades PTPN14, which results in decreased phosphorylation of LATS1 at T1079 and of YAP at S127, thereby inhibiting LATS1 kinase activity and activating YAP. PTPN14-dependent keratinocyte differentiation requires LATS kinases and certain PPxY motifs in PTPN14, but not MST1/2 or PTPN14 phosphatase active site. PTPN14 knockout, phospho-specific antibodies (LATS1 T1079, YAP S127), site-directed mutagenesis (PPxY motifs), keratinocyte differentiation assay mBio Medium 39248565
2022 TRIM65 promotes ubiquitination and proteasomal degradation of LATS1 in triple-negative breast cancer cells, promoting cell invasion and migration. Co-immunoprecipitation, cycloheximide chase, endogenous ubiquitination assay, rescue experiments Oxidative medicine and cellular longevity Low 36035221
2020 In Lats1/2-null intestinal epithelium, nuclear YAP/TAZ interact with Groucho/TLE to block Wnt/TCF-mediated transcription, inhibiting Wnt pathway activity. This YAP/TAZ-mediated Wnt inhibition is TEAD-independent. Conditional Lats1/2 knockout mice, chemical TEAD inhibitor, proteomics, nuclear co-immunoprecipitation of YAP/TAZ with TLE Cell stem cell Medium 32259481

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Tumor suppressor LATS1 is a negative regulator of oncogene YAP. The Journal of biological chemistry 675 18158288
2003 Hippo promotes proliferation arrest and apoptosis in the Salvador/Warts pathway. Nature cell biology 658 14502294
2007 The Salvador-Warts-Hippo pathway - an emerging tumour-suppressor network. Nature reviews. Cancer 558 17318211
2005 The Ste20-like kinase Mst2 activates the human large tumor suppressor kinase Lats1. Oncogene 503 15688006
2016 The Hippo Pathway Kinases LATS1/2 Suppress Cancer Immunity. Cell 365 27912060
2010 Lgl, aPKC, and Crumbs regulate the Salvador/Warts/Hippo pathway through two distinct mechanisms. Current biology : CB 289 20362447
1984 Cancer, warts, and sunshine in renal transplant patients. A case-control study. Lancet (London, England) 251 6143041
2010 Warts and Yorkie mediate intestinal regeneration by influencing stem cell proliferation. Current biology : CB 215 20727758
1989 Anal cancer incidence: genital warts, anal fissure or fistula, hemorrhoids, and smoking. Journal of the National Cancer Institute 211 2810388
2017 The LATS1 and LATS2 tumor suppressors: beyond the Hippo pathway. Cell death and differentiation 206 28644436
2008 The Fat and Warts signaling pathways: new insights into their regulation, mechanism and conservation. Development (Cambridge, England) 165 18697904
2020 Lats1/2 Sustain Intestinal Stem Cells and Wnt Activation through TEAD-Dependent and Independent Transcription. Cell stem cell 144 32259481
2021 A phosphatidic acid-binding lncRNA SNHG9 facilitates LATS1 liquid-liquid phase separation to promote oncogenic YAP signaling. Cell research 140 34267352
2002 LATS1 tumor suppressor regulates G2/M transition and apoptosis. Oncogene 136 11850843
1981 Identification of papillomaviruses in butchers' warts. The Journal of investigative dermatology 127 6257792
2014 The conserved misshapen-warts-Yorkie pathway acts in enteroblasts to regulate intestinal stem cells in Drosophila. Developmental cell 122 25453828
2017 The Hippo kinases LATS1 and 2 control human breast cell fate via crosstalk with ERα. Nature 121 28068668
2005 Human LATS1 is a mitotic exit network kinase. Cancer research 115 16061636
2023 The N6-methyladenosine METTL3 regulates tumorigenesis and glycolysis by mediating m6A methylation of the tumor suppressor LATS1 in breast cancer. Journal of experimental & clinical cancer research : CR 97 36609396
2007 Developing an HPV vaccine to prevent cervical cancer and genital warts. Vaccine 93 17289220
2007 The salvador-warts-hippo pathway is required for epithelial proliferation and axis specification in Drosophila. Current biology : CB 90 17964161
2022 WWC proteins mediate LATS1/2 activation by Hippo kinases and imply a tumor suppression strategy. Molecular cell 86 35429439
2019 miR-29c-3p regulates DNMT3B and LATS1 methylation to inhibit tumor progression in hepatocellular carcinoma. Cell death & disease 86 30718452
2014 HPV vaccines to prevent cervical cancer and genital warts: an update. Vaccine 84 24606637
2014 PTPN14 forms a complex with Kibra and LATS1 proteins and negatively regulates the YAP oncogenic function. The Journal of biological chemistry 78 25023289
2002 Molecular alterations of h-warts/LATS1 tumor suppressor in human soft tissue sarcoma. Laboratory investigation; a journal of technical methods and pathology 76 12379777
2015 Localization of Hippo signalling complexes and Warts activation in vivo. Nature communications 72 26420589
2009 HPV infection in women: psychosexual impact of genital warts and intraepithelial lesions. The journal of sexual medicine 72 19170869
2016 Lats1/2 Regulate Yap/Taz to Control Nephron Progenitor Epithelialization and Inhibit Myofibroblast Formation. Journal of the American Society of Nephrology : JASN 65 27647853
2019 LATS1 but not LATS2 represses autophagy by a kinase-independent scaffold function. Nature communications 54 31848340
2022 The Hippo pathway kinases LATS1 and LATS2 attenuate cellular responses to heavy metals through phosphorylating MTF1. Nature cell biology 53 35027733
2008 Warts is required for PI3K-regulated growth arrest, autophagy, and autophagic cell death in Drosophila. Current biology : CB 53 18818081
2015 Alterations in the NF2/LATS1/LATS2/YAP Pathway in Schwannomas. Journal of neuropathology and experimental neurology 52 26360373
2003 Topical immunomodulators for the treatment of external genital warts, cutaneous warts and molluscum contagiosum. The British journal of dermatology 52 14616340
2015 PARD3 induces TAZ activation and cell growth by promoting LATS1 and PP1 interaction. EMBO reports 50 26116754
1989 Anogenital warts in childhood. Child abuse & neglect 49 2545318
2010 LATS1 phosphorylates forkhead L2 and regulates its transcriptional activity. American journal of physiology. Endocrinology and metabolism 47 20407010
1981 Genital warts. Sexually transmitted diseases 45 6277022
2012 LATS1/WARTS phosphorylates MYPT1 to counteract PLK1 and regulate mammalian mitotic progression. The Journal of cell biology 44 22641346
1994 Cutaneous warts in butchers. The British journal of dermatology 44 8305325
2020 SPOP promotes ubiquitination and degradation of LATS1 to enhance kidney cancer progression. EBioMedicine 41 32460168
2018 Cell type-dependent function of LATS1/2 in cancer cell growth. Oncogene 41 30531839
2017 How I treat warts, hypogammaglobulinemia, infections, and myelokathexis syndrome. Blood 41 29066537
2019 Lats1 and Lats2 are required for ovarian granulosa cell fate maintenance. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 31268774
2015 Lats1 Deletion Causes Increased Germ Cell Apoptosis and Follicular Cysts in Mouse Ovaries. Biology of reproduction 36 26040669
2012 N-terminal truncation of Lats1 causes abnormal cell growth control and chromosomal instability. Journal of cell science 36 23230145
1984 Genital warts and cervical cancer. VI. The relationship between aneuploid and polyploid cervical lesions. American journal of obstetrics and gynecology 35 6089564
2018 Genital warts treatment: Beyond imiquimod. Human vaccines & immunotherapeutics 33 29505317
2010 Lgl/aPKC and Crb regulate the Salvador/Warts/Hippo pathway. Fly 33 20798605
2022 CD146 interaction with integrin β1 activates LATS1-YAP signaling and induces radiation-resistance in breast cancer cells. Cancer letters 30 35944750
1979 Immunology of human warts. Journal of the American Academy of Dermatology 30 229134
2013 Understanding genital warts: epidemiology, pathogenesis, and burden of disease of human papillomavirus. Journal of cutaneous medicine and surgery 29 24388558
2018 LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state. Life science alliance 28 30456386
2013 Human papillomavirus infections: warts or cancer? Cold Spring Harbor perspectives in biology 28 23685995
2022 Fibroblast growth factor 18 attenuates liver fibrosis and HSCs activation via the SMO-LATS1-YAP pathway. Pharmacological research 27 35202822
2021 Probiotic-prebiotic-synbiotic modulation of (YAP1, LATS1 and NF2 mRNAs/miR-1205/lncRNA SRD5A3-AS1) panel in NASH animal model. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 27 34090052
2019 PMEPA1 isoform a drives progression of glioblastoma by promoting protein degradation of the Hippo pathway kinase LATS1. Oncogene 27 31605013
1993 Anogenital warts in prepubertal children; sexual abuse or not? International journal of STD & AIDS 27 8218514
2023 WWP2 drives the progression of gastric cancer by facilitating the ubiquitination and degradation of LATS1 protein. Cell communication and signaling : CCS 26 36803368
2020 Intralesional immunotherapy for pediatric warts: A review. Pediatric dermatology 26 31930595
2016 Human papillomaviruses genotyping in plantar warts. Journal of medical virology 26 27736001
2019 LATS1/2 suppress NFκB and aberrant EMT initiation to permit pancreatic progenitor differentiation. PLoS biology 25 31323030
2017 Molecular Alterations and Expression Dynamics of LATS1 and LATS2 Genes in Non-Small-Cell Lung Carcinoma. Pathology oncology research : POR 25 28434174
2015 Immunomodulators in warts: Unexplored or ineffective? Indian journal of dermatology 25 25814698
2017 TNFAIP8 interacts with LATS1 and promotes aggressiveness through regulation of Hippo pathway in hepatocellular carcinoma. Oncotarget 24 28152516
2015 Lats1 suppresses centrosome overduplication by modulating the stability of Cdc25B. Scientific reports 24 26530630
2014 Sinecatechins (Polyphenon E) ointment for treatment of external genital warts and possible future indications. Expert opinion on biological therapy 24 24766274
2022 Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas. Nature communications 23 36443313
2020 Transcriptome analysis of HPV-induced warts and healthy skin in humans. BMC medical genomics 23 32151264
2019 A miRNA-HERC4 pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1. Protein & cell 23 30710319
2019 Photodynamic Therapy for Genital Warts Causes Activation of Local Immunity. Journal of cutaneous medicine and surgery 22 31010295
2018 A FUS-LATS1/2 Axis Inhibits Hepatocellular Carcinoma Progression via Activating Hippo Pathway. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 22 30308519
2017 LATS1 suppresses proliferation and invasion of cervical cancer. Molecular medicine reports 22 28259899
2015 17-AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway. Journal of cellular and molecular medicine 22 25712415
2021 LATS1 K751 acetylation blocks activation of Hippo signalling and switches LATS1 from a tumor suppressor to an oncoprotein. Science China. Life sciences 21 33945069
2006 Warts, cancer and ubiquitylation: lessons from the papillomaviruses. Transactions of the American Clinical and Climatological Association 21 18528468
2023 S1PR1 regulates ovarian cancer cell senescence through the PDK1-LATS1/2-YAP pathway. Oncogene 20 37828220
2022 LATS1 is a central signal transmitter for achieving full type-I interferon activity. Science advances 20 35394840
2017 TNFAIP8 regulates Hippo pathway through interacting with LATS1 to promote cell proliferation and invasion in lung cancer. Molecular carcinogenesis 20 28926138
2001 [Clinical aspects and therapy of anogenital warts and papillomavirus-associated lesions]. Der Hautarzt; Zeitschrift fur Dermatologie, Venerologie, und verwandte Gebiete 20 11220242
2014 TP53, MSH4, and LATS1 germline mutations in a family with clustering of nervous system tumors. The American journal of pathology 19 25041856
2024 LATS1/2 loss promote tumor immune evasion in endometrial cancer through downregulating MHC-I expression. Journal of experimental & clinical cancer research : CR 18 38383447
1988 Genital warts, papillomaviruses, and genital malignancies. Annual review of medicine 17 2835929
2019 Gα13-mediated LATS1 down-regulation contributes to epithelial-mesenchymal transition in ovarian cancer. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 14 31569999
2019 Lats1 and Lats2 are required for the maintenance of multipotency in the Müllerian duct mesenchyme. Development (Cambridge, England) 14 31575647
2016 Contribution of LATS1 and LATS2 promoter methylation in OSCC development. Journal of cell communication and signaling 14 27761802
2015 Phosphorylation of CHO1 by Lats1/2 regulates the centrosomal activation of LIMK1 during cytokinesis. Cell cycle (Georgetown, Tex.) 14 25786116
1993 Anogenital warts in children. Clinical and experimental dermatology 14 8394232
2023 A Comprehensive Review of Treatment Approaches for Cutaneous and Genital Warts. Cureus 13 38022045
2012 Control of tissue growth and cell transformation by the Salvador/Warts/Hippo pathway. PloS one 13 22359650
2024 METTL3 regulates cartilage development and homeostasis by affecting Lats1 mRNA stability in an m6A-YTHDF2-dependent manner. Cell reports 12 39088322
2023 Inhibition of EZH2 exerts antitumorigenic effects in renal cell carcinoma via LATS1. FEBS open bio 12 36808829
2022 TRIM65 Promotes Malignant Cell Behaviors in Triple-Negative Breast Cancer by Impairing the Stability of LATS1 Protein. Oxidative medicine and cellular longevity 12 36035221
2019 Salvador-Warts-Hippo pathway regulates sensory organ development via caspase-dependent nonapoptotic signaling. Cell death & disease 12 31511495
2000 Angiogenesis and vasodilation in skin warts. Association with HPV infection. Anticancer research 12 11205298
1998 Treatment of anogenital warts. Dermatologic clinics 12 9891689
2024 HPV18 E7 inhibits LATS1 kinase and activates YAP1 by degrading PTPN14. mBio 11 39248565
2022 LATS1/2 control TGFB-directed epithelial-to-mesenchymal transition in the murine dorsal cranial neuroepithelium through YAP regulation. Development (Cambridge, England) 11 36125128
2021 Intralesional Acyclovir: A Potential Therapeutic Option for Cutaneous Warts. Journal of cutaneous medicine and surgery 11 34412535
2020 Targeted Disruption of Lats1 and Lats2 in Mice Impairs Adrenal Cortex Development and Alters Adrenocortical Cell Fate. Endocrinology 11 32243503

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