Affinage

LATS2

Serine/threonine-protein kinase LATS2 · UniProt Q9NRM7

Length
1088 aa
Mass
120.1 kDa
Annotated
2026-06-10
100 papers in source corpus 34 papers cited in narrative 34 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LATS2 is a serine/threonine kinase that functions as the catalytic effector of the Hippo tumor-suppressor pathway and as a broader guardian of genomic integrity and cell-fate control (PMID:12853976, PMID:21245096). Its kinase activity requires dual phosphorylation of the T-loop (Ser872) and the hydrophobic motif (Thr1041), the latter installed by MST1/2, with MOB1 binding supporting both events; this activated kinase phosphorylates and inactivates the transcriptional co-activators YAP/TAZ to restrict their nuclear oncogenic output (PMID:26898830, PMID:21245096). LATS2 activation is spatially organized: angiomotin-family scaffolds (AMOT/AMOTL1/AMOTL2) cluster LATS2 with MST2 and YAP at tight junctions at high cell density (PMID:21832154), and loss of F-actin drives LATS2 into proline-rich-motif-dependent biomolecular condensates that assemble a Hippo signalosome, activate the kinase, and sequester YAP/TAZ (PMID:38200110). Beyond YAP/TAZ, LATS2 directly phosphorylates a diverse substrate set to enforce stress responses and growth arrest: ASPP1 (directing p53 to proapoptotic promoters) (PMID:21041410), p21/CDKN1A at Ser146 to promote its degradation and UV-induced apoptosis (PMID:23886938), Snail1 at Thr203 to drive its nuclear retention and EMT (PMID:21952048), c-Abl to suppress DNA-damage apoptosis at high density (PMID:23852372), DYRK1A to assemble the DREAM complex and enforce pRB-dependent senescence (PMID:21498571), and MTF1 to attenuate the heavy-metal response independently of YAP/TAZ (PMID:35027733). LATS2 also restrains Wnt signaling kinase-independently by disrupting the β-catenin/BCL9 interaction (PMID:24360964) and limits SREBP-driven hepatic cholesterol metabolism (PMID:27013235). The kinase enforces mitotic fidelity through centrosomal and spindle functions, with knockout causing centrosome amplification and cytokinesis failure (PMID:15343267, PMID:17478426). Its abundance and activity are tightly tuned by phosphorylation (Aurora-A, Chk1/Chk2), O-GlcNAcylation at Thr436 (which uncouples MOB1), HSP90 chaperoning, USP9X deubiquitylation, and Siah2/Zyxin- and FBXL16-mediated degradation, as well as a YAP-TEAD transcriptional feedback loop (PMID:15147269, PMID:21118956, PMID:32513743, PMID:20841485, PMID:29183995, PMID:27030211, PMID:38200110, PMID:27006470). Re-expression studies establish LATS2 as a tumor suppressor in malignant mesothelioma and other contexts, frequently silenced by promoter hypermethylation (PMID:21245096, PMID:19855428).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2000 Medium

    Established the basic identity and chromosomal context of LATS2, placing it at a locus of frequent cancer-associated loss and hinting at a tumor-suppressor role.

    Evidence Cell fractionation/immunoblotting and FISH mapping in human cells

    PMID:10673337

    Open questions at the time
    • No functional activity demonstrated
    • Nuclear localization not reconciled with later mitotic/centrosomal findings
  2. 2003 High

    Demonstrated that LATS2 is a kinase-dependent growth suppressor controlling G1/S transition and tumor formation, defining its core tumor-suppressor function and essential domains.

    Evidence Retroviral overexpression in NIH3T3/v-ras, cell cycle profiling, CDK2 kinase assay, domain-deletion mutants, nude mouse tumor assay

    PMID:12853976

    Open questions at the time
    • Direct substrates not identified
    • Mechanism linking kinase activity to cyclin E/CDK2 downregulation unresolved
  3. 2004 High

    Connected LATS2 to mitotic apparatus and centrosome biology, showing it is required for genomic integrity and is regulated by Aurora-A phosphorylation, and that it can trigger intrinsic apoptosis.

    Evidence Lats2 knockout mouse and MEFs, Aurora-A in vitro/in vivo phospho-mapping (Ser83), co-IP, immunofluorescence, adenoviral overexpression with apoptosis assays

    PMID:15131260 PMID:15147269 PMID:15265683 PMID:15343267

    Open questions at the time
    • Substrates at the centrosome not defined
    • Relationship between AR repression and kinase activity unclear
  4. 2006 High

    Identified Ajuba as a mitotic LATS2 partner and substrate required for spindle formation, linking LATS2 kinase activity to centrosome maturation.

    Evidence Yeast two-hybrid, co-IP, siRNA depletion, gamma-tubulin/spindle immunofluorescence

    PMID:16413547

    Open questions at the time
    • Ajuba phosphosite not mapped
    • Functional consequence of phosphorylation on gamma-tubulin recruitment not dissected
  5. 2007 High

    Established that MOB1-family proteins associate with and activate LATS2, and confirmed in vivo essentiality through knockout lethality with mitotic defects.

    Evidence Lats2 knockout mouse, MEF phenotyping, Lats2-MOB1 co-IP, immunofluorescence

    PMID:17478426

    Open questions at the time
    • MOB1-binding interface on LATS2 not mapped here
    • Mechanism of activation by MOB1 not yet biochemically defined
  6. 2008 High

    Placed LATS2 downstream of MST1 in a physiological organ context (heart) and showed it relays growth/apoptosis signals, and linked it to YAP2/p73-dependent DNA-damage gene induction.

    Evidence Cardiac transgenic and dominant-negative mice with morphometry; co-expression, p73 stability, PUMA-promoter ChIP, kinase-dead mutant in leukemic cells

    PMID:18565851 PMID:18927464

    Open questions at the time
    • Direct cardiac substrates not identified
    • Reconciliation of YAP2 stabilization with later YAP-inactivation model not addressed
  7. 2009 High

    Defined a stress-checkpoint role in which oncogene-induced ATR-Chk1 signaling relocalizes and stabilizes LATS2 to activate p53, and showed promoter hypermethylation as an escape mechanism.

    Evidence Oncogenic H-Ras expression, localization immunofluorescence, qPCR, methylation analysis, death/senescence assays

    PMID:19855428

    Open questions at the time
    • Direct LATS2 substrate driving p53 activation not pinned down here
    • Quantitative contribution of methylation in human tumors unresolved
  8. 2010 High

    Expanded the LATS2 substrate/regulator network in stress responses (Chk1/Chk2-LATS2-14-3-3γ P-body axis, ASPP1-p53 proapoptotic targeting) and identified post-transcriptional control by TTP and chaperoning by HSP90.

    Evidence Phosphosite mapping, kinase assays, siRNA, P-body and apoptosis assays; REMSA/luciferase for TTP; co-IP and kinase assay with HSP90 inhibition

    PMID:20335167 PMID:20841485 PMID:21041410 PMID:21118956

    Open questions at the time
    • Hierarchy among competing regulatory inputs not established
    • In vivo relevance of 14-3-3γ/P-body axis not tested
  9. 2011 High

    Broadened LATS2 substrate scope into senescence (DYRK1A/DREAM), EMT (Snail1 Thr203), and mitotic accuracy (Aurora-A Ser380 axis), and defined density-dependent activation via angiomotins at tight junctions; confirmed tumor suppression via YAP inactivation in mesothelioma.

    Evidence shRNA screens, in vitro kinase assays with site mapping, ChIP, phospho-antibodies, mutant phenotyping, co-IP, multi-organism EMT models, MM cell rescue

    PMID:21245096 PMID:21498571 PMID:21822051 PMID:21832154 PMID:21952048

    Open questions at the time
    • How a single kinase selects among diverse substrates in different contexts unclear
    • Spatial coordination of mitotic vs Hippo functions unresolved
  10. 2013 High

    Revealed kinase-independent (Wnt/β-catenin-BCL9) and additional kinase-dependent (p21 Ser146, c-Abl) functions, showing LATS2 integrates UV/DNA-damage and cell-density signals into apoptotic decisions.

    Evidence Co-IP, ChIP, kinase-dead and in vitro kinase assays, knockdown, caspase and apoptosis assays, tumor models

    PMID:23852372 PMID:23886938 PMID:24360964

    Open questions at the time
    • Switch between proapoptotic and antiapoptotic outputs context-dependence not mechanistically resolved
    • Structural basis of β-catenin/BCL9 disruption unknown
  11. 2016 High

    Resolved the biochemical activation logic (Ser872 + Thr1041, MST1/2, MOB1) and uncovered multiple layers of abundance control (Siah2/Zyxin degradation, YAP-TEAD feedback) plus a YAP-independent metabolic role via SREBP2.

    Evidence Phosphomimetic/ablating variants and kinase assays; co-IP and ubiquitination assays; ChIP/reporter and in vivo liver knockouts; interactor screen with conditional knockout metabolic phenotyping

    PMID:26898830 PMID:27006470 PMID:27013235 PMID:27030211

    Open questions at the time
    • Structural model of the active kinase not provided
    • Crosstalk between metabolic and Hippo outputs not integrated
  12. 2017 High

    Identified opposing post-translational regulators of LATS2 stability/activity (JCAD inhibition; USP9X deubiquitylation) that tune YAP/TAZ output in cancer.

    Evidence Co-IP, kinase inhibition assays, TAP, ubiquitination and protein-stability assays, knockdown

    PMID:28775168 PMID:29183995

    Open questions at the time
    • E3 ligase counteracted by USP9X not fully defined here
    • JCAD-LATS2 binding interface not mapped structurally
  13. 2019 High

    Demonstrated that the LATS2-YAP1 negative feedback loop acts as a cell-fate switch, with LATS2 enforcing senescence and its loss permitting YAP-driven transformation.

    Evidence LATS2 siRNA/CRISPR deletion, YAP1 overexpression, SA-β-gal senescence and transformation assays in primary hOSEs

    PMID:30755404

    Open questions at the time
    • Threshold setting the senescence-vs-transformation switch unknown
    • Downstream senescence effectors not enumerated
  14. 2020 High

    Showed that O-GlcNAcylation at Thr436 inactivates LATS2 by uncoupling MOB1, providing a metabolic-to-Hippo signaling link that hyperactivates YAP/TAZ.

    Evidence Mass spectrometry site ID, T436A mutagenesis, MOB1-LATS2 co-IP, YAP/TAZ phosphorylation western blot in breast cancer cells

    PMID:32513743

    Open questions at the time
    • O-GlcNAc transferase responsible not defined here
    • In vivo contribution to tumorigenesis not established
  15. 2021 High

    Uncovered a LATS2-mTORC1-autophagy axis in pancreatic β-cells, expanding LATS2 function into metabolic-stress-induced apoptosis and revealing it is itself an autophagy substrate.

    Evidence β-cell-specific Lats2 knockout mice, rapamycin rescue, autophagy flux and apoptosis assays, insulin secretion measurement

    PMID:34389720

    Open questions at the time
    • Direct mTORC1-pathway substrate of LATS2 not identified
    • Relationship of this axis to canonical Hippo signaling unclear
  16. 2022 High

    Established a YAP/TAZ-independent function in which LATS phosphorylates and inhibits MTF1, with zinc directly binding and inhibiting LATS, positioning LATS2 as a sensor in the heavy-metal stress response.

    Evidence In vitro kinase assay, zinc-binding assay, Hippo-deficient cells, transcriptional reporters, metal-stress viability assays

    PMID:35027733

    Open questions at the time
    • MTF1 phosphosite(s) and LATS2-specific contribution vs LATS1 not delineated
    • Structural basis of zinc inhibition unknown
  17. 2024 High

    Defined the spatial/biophysical basis of LATS2 activation by showing F-actin loss drives PRM-dependent condensation into a Hippo signalosome that activates the kinase, sequesters YAP/TAZ, and is antagonized by FBXL16-mediated degradation.

    Evidence Live-cell condensate imaging, PRM mutants, FBXL16-LATS2 co-IP, ubiquitination assay, kinase/YAP-TAZ phosphorylation readouts, tumor models

    PMID:38200110

    Open questions at the time
    • Condensate composition and material properties not fully characterized
    • How cytoskeletal sensing is transduced to the PRM unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How LATS2 selects among its many substrates and switches between pro- and anti-apoptotic, kinase-dependent and kinase-independent outputs across cellular contexts remains the central open question.
  • No integrated structural model of the active LATS2 kinase with its scaffolds
  • Quantitative rules governing context-specific substrate choice unknown
  • In vivo importance of individual non-YAP substrates largely untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016740 transferase activity 5 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005634 nucleus 3 GO:0005815 microtubule organizing center 3 GO:0005886 plasma membrane 2 GO:0005829 cytosol 1
Pathway
R-HSA-5357801 Programmed Cell Death 5 R-HSA-162582 Signal Transduction 4 R-HSA-1640170 Cell Cycle 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-1430728 Metabolism 2
Partners
AMOTL2AURKAMOB1MST1/2SREBP2USP9XYAP1ZYXIN
Complex memberships
DREAM complex (functional link)Hippo signalosome (LATS2 condensate)

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 LATS2 protein localizes to the nucleus in human cells, as determined by immunoblotting of fractionated cell lysates; the gene maps to chromosome 13q11-q12, a region of frequent LOH in cancers. Cell fractionation and immunoblotting; fluorescence in situ hybridization Genomics Medium 10673337
2003 Ectopic Lats2 expression inhibits G1/S transition, downregulates cyclin E/CDK2 kinase activity, suppresses tumor formation in athymic nude mice, and requires LATS2 kinase activity and two conserved LATS domains (LCDs) for its growth-suppressive function. During interphase LATS2 is cytoplasmic; during mitosis it localizes to the mitotic apparatus. Retroviral overexpression in NIH3T3/v-ras cells, cell cycle profiling, kinase activity assay, subcellular localization by immunofluorescence, nude mouse tumor assay Oncogene High 12853976
2004 Aurora-A kinase directly phosphorylates LATS2 at Ser83 in vitro and in vivo; LATS2 and Aurora-A transiently interact and co-localize at centrosomes during the cell cycle; inhibiting S83 phosphorylation partially perturbs centrosomal localization of LATS2. In vitro kinase assay with phospho-specific antibody, co-immunoprecipitation, immunofluorescence co-localization Genes to cells High 15147269
2004 Lats2 overexpression induces apoptosis in lung cancer cells via the intrinsic caspase-9 pathway, accompanied by downregulation of anti-apoptotic proteins BCL-2 and BCL-xL (but not BAX); overexpression of BCL-2 or BCL-xL suppresses Lats2-mediated apoptosis. Adenoviral overexpression, Annexin V, PARP cleavage, DNA laddering, caspase inhibitor rescue, western blot Experimental cell research High 15265683
2004 LATS2 is required for embryonic development and genomic integrity; Lats2-/- mouse embryos show centrosome amplification and defective cytokinesis; Lats2 localizes to centrosomes and its overexpression suppresses centrosome overduplication. Lats2 knockout mouse, MEF analysis, immunofluorescence for centrosome localization, centrosome amplification assay The EMBO journal High 15343267
2004 LATS2 interacts with the androgen receptor (AR) ligand-binding domain, inhibits androgen-regulated gene expression including PSA, and represses AR NH2-/COOH-terminal interaction; LATS2 and AR co-occupy PSA promoter/enhancer regions. Co-immunoprecipitation, reporter assay, chromatin immunoprecipitation, endogenous PSA mRNA measurement Molecular endocrinology High 15131260
2006 LATS2 interacts with the LIM protein Ajuba during mitosis; the LATS2-Ajuba complex is required for gamma-tubulin recruitment to centrosomes and proper spindle formation; LATS2 phosphorylates Ajuba during mitosis. Yeast two-hybrid, co-immunoprecipitation, siRNA depletion, immunofluorescence for gamma-tubulin and spindle markers FEBS letters High 16413547
2007 Complete Lats2 knockout in mice causes lethality with nervous system defects; knockout cells show centrosome fragmentation, cytokinesis failure, and accelerated mitotic exit; MOB1 family proteins associate with Lats2 and promote its activation. Lats2 knockout mouse, MEF phenotypic analysis, co-immunoprecipitation of Lats2-MOB1 interaction, immunofluorescence The Journal of biological chemistry High 17478426
2008 Lats2 mediates cardiac myocyte growth inhibition downstream of Mst1; dominant-negative Lats2 attenuates Mst1-induced apoptosis and inhibition of hypertrophy; cardiac-specific Lats2 transgenic mice show reduced ventricular size, while DN-Lats2 transgenic mice develop hypertrophy. Adenoviral overexpression, dominant-negative mutant, transgenic mice, phenylalanine incorporation assay, cardiac morphometry Circulation research High 18927464
2009 Oncogenic H-Ras activates an ATR-Chk1-mediated stress checkpoint that triggers Lats2 translocation from centrosomes to the nucleus with increased Lats2 protein levels, leading to p53 activation, proapoptotic gene induction, and apoptosis/senescence; cells that escape this checkpoint show reduced Lats2 levels associated with Lats2 promoter hypermethylation. Oncogenic H-Ras expression, immunofluorescence for subcellular localization, qPCR for gene expression, methylation analysis, cell death and senescence assays Oncogene High 19855428
2010 Lats2 is phosphorylated by Chk1 (predominantly) and Chk2 at S408 in response to UV radiation; phosphorylated Lats2 in turn phosphorylates 14-3-3γ at S59; phosphorylated 14-3-3γ translocates to P-bodies; depletion of Lats2 or 14-3-3γ inhibits UV-induced P-body formation. In vivo phosphorylation mapping, immunoprecipitation/western blot, siRNA knockdown, immunofluorescence for P-body markers Journal of cell science High 21118956
2010 LATS2 mRNA is a direct target of the RNA-binding protein tristetraprolin (TTP); TTP binds AU-rich elements in the LATS2 3'UTR and promotes LATS2 mRNA decay; TTP overexpression reduces LATS2 protein levels, while TTP knockdown stabilizes LATS2 mRNA and suppresses cancer cell proliferation. RNA electrophoretic mobility shift assay (REMSA), luciferase reporter assay with LATS2 AREs, siRNA knockdown, western blot, proliferation assay The Journal of biological chemistry High 20335167
2010 Lats2 phosphorylates ASPP1 in response to oncogenic stress, driving ASPP1 nuclear translocation; nuclear ASPP1 together with Lats2 directs p53 to proapoptotic promoters and promotes death of polyploid cells; YAP1 disrupts Lats2-ASPP1 binding and antagonizes this tumor-suppressive axis. Co-immunoprecipitation, in vitro kinase assay (Lats2 phosphorylating ASPP1), immunofluorescence for ASPP1 localization, reporter assay, apoptosis assay Genes & development High 21041410
2010 LATS1 and LATS2 interact with HSP90; HSP90 inhibition depletes both kinases via the proteasome, reduces LATS1 catalytic activity, and disrupts downstream YAP phosphorylation; LATS1/2 are bona fide HSP90 client proteins. Co-immunoprecipitation with HSP90, in vitro kinase assay after HSP90 inhibitor treatment, western blot in cells and clinical specimens Cancer research High 20841485
2011 Angiomotin-family proteins AMOT, AMOTL1, and AMOTL2 activate LATS2 through a conserved domain; AMOTL2 serves as a scaffold binding MST2, LATS2, and YAP; LATS2, AMOTL2, and YAP co-localize at tight junctions, suggesting tight junction clustering triggers LATS2 activation at high cell density. Co-immunoprecipitation, kinase activation assay, immunofluorescence for tight junction co-localization Molecular biology of the cell High 21832154
2011 LATS2 cooperates with pRB to silence E2F target genes and promote DREAM complex assembly; LATS2 phosphorylates DYRK1A, which in turn phosphorylates the DREAM subunit LIN52; partial LATS2 knockdown suppresses pRB-induced senescence markers. shRNA screen, kinase assay (LATS2 phosphorylating DYRK1A; DYRK1A phosphorylating LIN52), DREAM complex ChIP, gene expression analysis Genes & development High 21498571
2011 Aurora A phosphorylates Lats2 at Ser380 during mitosis; S380-phosphorylated Lats2 co-localizes at the central spindle with Aurora B; Lats1 phosphorylates Aurora B; the Aurora A-Lats1/2-Aurora B axis regulates accurate mitotic progression; cells expressing non-phosphorylatable S380A Lats2 show chromosome missegregation and cytokinesis failure. In vitro kinase assay, phospho-specific antibody, immunocytochemistry, co-immunoprecipitation, mutant expression analysis Cell cycle High 21822051
2011 LATS2 is a tumor suppressor in malignant mesothelioma; re-expression of LATS2 in MM cells phosphorylates and inactivates YAP, inhibiting MM cell growth. LATS2 transduction in MM cell lines, western blot for YAP phosphorylation, proliferation assay Cancer research High 21245096
2011 Lats2 kinase interacts with Snail1 and directly phosphorylates Snail1 at Thr203 in the nucleus, promoting Snail1 nuclear retention and stability, enhancing EMT and tumor cell invasion in a Snail1-dependent manner; during TGFβ-induced EMT, Lats2 is activated and Snail1 is phosphorylated at T203. Live-cell bioluminescence kinome RNAi screen, co-immunoprecipitation, in vitro kinase assay, immunofluorescence, mouse and zebrafish in vivo studies The EMBO journal High 21952048
2013 LATS2 inhibits oncogenic Wnt/β-catenin transcription by directly interacting with β-catenin and disrupting the β-catenin/BCL9 interaction, independent of LATS2 kinase activity; LATS2 is present on Wnt target gene promoters. Co-immunoprecipitation, ChIP, reporter assay, kinase-dead mutant, in vivo tumor model with nocodazole Cell reports High 24360964
2013 Lats2 phosphorylates p21/CDKN1A at S146 in response to UV irradiation; this phosphorylation is preceded by Chk1-mediated phosphorylation of Lats2 at Ser835 (which activates Lats2 kinase); Lats2-mediated p21 phosphorylation induces p21 degradation, caspase-3 and -9 activation, and apoptosis. In vitro kinase assay, phospho-specific antibodies, overexpression/knockdown, caspase activity assay, western blot Journal of cell science High 23886938
2013 At high cell density, active Lats2 inhibits c-Abl tyrosine kinase activity through direct interaction and phosphorylation of c-Abl, reducing phosphorylation of YAP and p73, and suppressing DNA damage-induced apoptosis; Lats2 knockdown restores c-Abl activity and apoptosis in dense cells. Co-immunoprecipitation, in vitro kinase assay for Lats2-c-Abl interaction, phospho-substrate western blot, siRNA knockdown, apoptosis assay Cell death and differentiation High 23852372
2016 LATS2 kinase activation requires phosphorylation of both Ser872 (T-loop) and Thr1041 (hydrophobic motif); MST1/2 phosphorylate LATS2 on Thr1041 but not Ser872; MOB1 binding to LATS2 supports both phosphorylation events; a hyperactive LATS2-PIF variant phosphorylates YAP1 and inhibits its transcriptional co-activity dependent on LATS2 kinase activity but independent of MOB1/LATS2 or YAP1/LATS2 complex formation. Phosphomimetic and phosphoablating LATS2 variants, in vitro kinase assay, MOB1/LATS2 interaction assays, YAP1 transcriptional reporter assay Cellular signalling High 26898830
2016 Zyxin acts as a scaffold forming a ternary complex with Lats2 and the E3 ubiquitin ligase Siah2 in response to hypoxia and TGF-β stimuli, facilitating Lats2 ubiquitination and proteasomal degradation, thereby decreasing Hippo signaling and activating YAP. Co-immunoprecipitation, ubiquitination assay, Lats2 protein stability assay, siRNA knockdown of Zyxin, in vivo xenograft Nature communications High 27030211
2016 Activated YAP, together with TEAD transcription factors, directly induces transcription of LATS2 (but not LATS1), forming an evolutionarily conserved negative feedback loop; this feedback is functionally relevant as Lats2 deletion in a Sav1-knockout mouse liver model severely enhances YAP-induced tumorigenesis. ChIP/reporter assay for YAP-TEAD on LATS2 promoter, Lats2-specific knockout in vivo, soft agar assay, Drosophila ortholog validation Oncotarget High 27006470
2016 LATS2 interacts with the transcription factor SREBP2 (master regulator of cholesterol homeostasis); LATS2 depletion activates SREBP and causes hepatic cholesterol accumulation; liver-specific Lats2 conditional knockout mice develop spontaneous fatty liver disease with constitutive SREBP activation, and show impaired p53 activation and failure to recover from cholesterol-induced damage. Screen for LATS2-interacting proteins, co-immunoprecipitation, liver-specific conditional knockout mouse, western blot, gene expression analysis Genes & development High 27013235
2017 JCAD interacts with the kinase domain of LATS2 and inhibits LATS2-mediated phosphorylation of YAP, thereby upregulating CCND1 and GLI2 to promote hepatoma cell proliferation. Co-immunoprecipitation, kinase assay (LATS2 phosphorylating YAP in presence/absence of JCAD), western blot, JCAD overexpression/knockdown Cancer research High 28775168
2017 USP9X deubiquitylates LATS2 and prevents its proteasomal degradation; anaphase-promoting complex/cyclosome (APC/C) interacts with LATS2 but does not regulate its protein levels or activity; USP9X ablation activates YAP/TAZ and enhances oncogenic potential of pancreatic cancer cells. Tandem affinity purification (TAP), co-immunoprecipitation, ubiquitination assay, USP9X knockdown, protein stability assay The Journal of biological chemistry High 29183995
2019 YAP1 hyperactivation induces cellular senescence in human ovarian surface epithelial cells; LATS2 is elevated in both YAP1-induced and replicative senescence; deletion of LATS2 in hOSEs prevents senescence and switches YAP-induced senescence to malignant transformation, demonstrating a LATS2-YAP1 negative feedback loop controlling cell fate. LATS2 siRNA/CRISPR deletion, YAP1 overexpression, senescence assays (SA-β-gal), transformation assays in primary hOSEs EMBO reports High 30755404
2020 O-GlcNAcylation of LATS2 at Thr436 disrupts its interaction with the MOB1 adaptor protein, preventing MST-to-LATS2 signal relay, suppressing LATS2 kinase activity, and consequently hyperactivating YAP/TAZ in breast cancer cells. Mass spectrometry identification of O-GlcNAc site, site-directed mutagenesis (T436A), co-immunoprecipitation of MOB1-LATS2 interaction, YAP/TAZ phosphorylation western blot Proceedings of the National Academy of Sciences of the United States of America High 32513743
2021 LATS2 activates mTORC1 in pancreatic β-cells, suppressing autophagy; LATS2 is itself an autophagy substrate; LATS2 deficiency improves β-cell viability, insulin secretion, and β-cell mass under diabetic conditions; genetic and pharmacological mTORC1 inhibition counteracts LATS2-induced β-cell apoptosis. β-cell-specific Lats2 knockout mice, mTORC1 inhibitor (rapamycin), autophagy flux assay, apoptosis assay, insulin secretion measurement Nature communications High 34389720
2022 LATS kinases phosphorylate and inhibit MTF1 (metal-responsive transcription factor 1), attenuating heavy metal response gene transcription; this function is independent of YAP/TAZ; zinc directly binds LATS and inhibits its kinase activity following heavy metal treatment. In vitro kinase assay (LATS phosphorylating MTF1), zinc binding to LATS, Hippo-deficient cell lines, transcriptional reporter assay, cell viability under metal stress Nature cell biology High 35027733
2024 LATS2 forms biomolecular condensates in response to F-actin cytoskeleton reduction, mediated by its proline-rich motif (PRM); these condensates assemble a signalosome with core Hippo pathway components, activating LATS2 and protecting it from FBXL16 E3-ligase-dependent degradation; condensation recruits and inactivates YAP/TAZ; the oncogenic FBXL16 complex blocks LATS2 condensation by binding the PRM, promoting LATS2 degradation. Live-cell imaging of condensate formation, PRM deletion/mutation, co-immunoprecipitation of FBXL16-LATS2, ubiquitination assay, LATS2 kinase activity and YAP/TAZ phosphorylation assays, tumor progression models Nature chemical biology High 38200110
2008 Kpm/Lats2 stabilizes YAP2 (through YAP2 phosphorylation at Ser127) and p73 in leukemic cells; Lats2 kinase activity and YAP2 phosphorylation are required for nuclear accumulation of p73, its recruitment to the PUMA promoter, and induction of p21/PUMA expression in response to DNA damage. Co-expression studies, western blot for p73 stability, chromatin immunoprecipitation for p73 at PUMA promoter, Lats2 knockdown/overexpression, kinase-dead mutant Blood High 18565851

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 m6A demethylase ALKBH5 inhibits tumor growth and metastasis by reducing YTHDFs-mediated YAP expression and inhibiting miR-107/LATS2-mediated YAP activity in NSCLC. Molecular cancer 293 32106857
2005 Down-regulation of LATS1 and LATS2 mRNA expression by promoter hypermethylation and its association with biologically aggressive phenotype in human breast cancers. Clinical cancer research : an official journal of the American Association for Cancer Research 263 15746036
2016 Long Noncoding RNA PVT1 Promotes Non-Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression. Molecular cancer therapeutics 216 26908628
2017 The LATS1 and LATS2 tumor suppressors: beyond the Hippo pathway. Cell death and differentiation 206 28644436
2011 LATS2 is a tumor suppressor gene of malignant mesothelioma. Cancer research 196 21245096
2004 Lats2/Kpm is required for embryonic development, proliferation control and genomic integrity. The EMBO journal 178 15343267
2012 MiR-93 enhances angiogenesis and metastasis by targeting LATS2. Cell cycle (Georgetown, Tex.) 171 23111389
2011 Angiomotin family proteins are novel activators of the LATS2 kinase tumor suppressor. Molecular biology of the cell 168 21832154
2003 Lats2, a putative tumor suppressor, inhibits G1/S transition. Oncogene 167 12853976
2016 Upregulated long non-coding RNA AGAP2-AS1 represses LATS2 and KLF2 expression through interacting with EZH2 and LSD1 in non-small-cell lung cancer cells. Cell death & disease 151 27195672
2006 Promoter hypermethylation-mediated down-regulation of LATS1 and LATS2 in human astrocytoma. Neuroscience research 140 17049657
2007 Lats2 is an essential mitotic regulator required for the coordination of cell division. The Journal of biological chemistry 131 17478426
2009 miR-372 regulates cell cycle and apoptosis of ags human gastric cancer cell line through direct regulation of LATS2. Molecules and cells 121 19937137
2004 The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase. Genes to cells : devoted to molecular & cellular mechanisms 121 15147269
2008 Lats2 is a negative regulator of myocyte size in the heart. Circulation research 115 18927464
2011 A kinase shRNA screen links LATS2 and the pRB tumor suppressor. Genes & development 108 21498571
2000 Structure, expression, and chromosome mapping of LATS2, a mammalian homologue of the Drosophila tumor suppressor gene lats/warts. Genomics 97 10673337
2011 Lats2 kinase potentiates Snail1 activity by promoting nuclear retention upon phosphorylation. The EMBO journal 96 21952048
2016 The LATS2 tumor suppressor inhibits SREBP and suppresses hepatic cholesterol accumulation. Genes & development 95 27013235
2018 Long noncoding RNA PCAT6 functions as an oncogene by binding to EZH2 and suppressing LATS2 in non-small-cell lung cancer. EBioMedicine 94 30314898
2010 The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1. Genes & development 88 21041410
2016 Zyxin-Siah2-Lats2 axis mediates cooperation between Hippo and TGF-β signalling pathways. Nature communications 86 27030211
2004 Putative tumor suppressor Lats2 induces apoptosis through downregulation of Bcl-2 and Bcl-x(L). Experimental cell research 84 15265683
2006 LATS2-Ajuba complex regulates gamma-tubulin recruitment to centrosomes and spindle organization during mitosis. FEBS letters 82 16413547
2018 Long noncoding RNA MEG3 regulates LATS2 by promoting the ubiquitination of EZH2 and inhibits proliferation and invasion in gallbladder cancer. Cell death & disease 76 30282996
2022 m6A methyltransferase METTL3-induced lncRNA SNHG17 promotes lung adenocarcinoma gefitinib resistance by epigenetically repressing LATS2 expression. Cell death & disease 74 35902569
2016 miR-135b, upregulated in breast cancer, promotes cell growth and disrupts the cell cycle by regulating LATS2. International journal of oncology 69 26934863
2017 miR-302/367/LATS2/YAP pathway is essential for prostate tumor-propagating cells and promotes the development of castration resistance. Oncogene 67 28745315
2020 Exosomal miR-135a derived from human amnion mesenchymal stem cells promotes cutaneous wound healing in rats and fibroblast migration by directly inhibiting LATS2 expression. Stem cell research & therapy 66 32054526
2016 Co-occurring Mutations of Tumor Suppressor Genes, LATS2 and NF2, in Malignant Pleural Mesothelioma. Clinical cancer research : an official journal of the American Association for Cancer Research 66 28003305
2019 Irisin ameliorates septic cardiomyopathy via inhibiting DRP1-related mitochondrial fission and normalizing the JNK-LATS2 signaling pathway. Cell stress & chaperones 63 30993599
2018 RASAL2 promotes tumor progression through LATS2/YAP1 axis of hippo signaling pathway in colorectal cancer. Molecular cancer 63 30037330
2014 MiR-25 promotes ovarian cancer proliferation and motility by targeting LATS2. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 63 25179841
2019 YAP1-LATS2 feedback loop dictates senescent or malignant cell fate to maintain tissue homeostasis. EMBO reports 62 30755404
2017 JCAD Promotes Progression of Nonalcoholic Steatohepatitis to Liver Cancer by Inhibiting LATS2 Kinase Activity. Cancer research 62 28775168
2013 Lats2 modulates adipocyte proliferation and differentiation via hippo signaling. PloS one 62 23977200
2010 Heat shock protein 90 inhibition depletes LATS1 and LATS2, two regulators of the mammalian hippo tumor suppressor pathway. Cancer research 62 20841485
2016 The characterisation of LATS2 kinase regulation in Hippo-YAP signalling. Cellular signalling 61 26898830
2019 miR-25 Promotes Cell Proliferation, Migration, and Invasion of Non-Small-Cell Lung Cancer by Targeting the LATS2/YAP Signaling Pathway. Oxidative medicine and cellular longevity 59 31316723
2013 The Hippo pathway kinase Lats2 prevents DNA damage-induced apoptosis through inhibition of the tyrosine kinase c-Abl. Cell death and differentiation 59 23852372
2013 LATS2 suppresses oncogenic Wnt signaling by disrupting β-catenin/BCL9 interaction. Cell reports 59 24360964
2009 Silencing of the Lats2 tumor suppressor overrides a p53-dependent oncogenic stress checkpoint and enables mutant H-Ras-driven cell transformation. Oncogene 59 19855428
2019 The Hippo Kinase LATS2 Controls Helicobacter pylori-Induced Epithelial-Mesenchymal Transition and Intestinal Metaplasia in Gastric Mucosa. Cellular and molecular gastroenterology and hepatology 58 31669263
2011 The tumor suppressor Lats2 is pivotal in Aurora A and Aurora B signaling during mitosis. Cell cycle (Georgetown, Tex.) 56 21822051
2016 Long non-coding RNA CCAT2 promotes gastric cancer proliferation and invasion by regulating the E-cadherin and LATS2. American journal of cancer research 55 27904778
2004 The LATS2/KPM tumor suppressor is a negative regulator of the androgen receptor. Molecular endocrinology (Baltimore, Md.) 55 15131260
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
2017 Downregulation of MiR-31 stimulates expression of LATS2 via the hippo pathway and promotes epithelial-mesenchymal transition in esophageal squamous cell carcinoma. Journal of experimental & clinical cancer research : CR 52 29145896
2017 Deubiquitylase USP9X suppresses tumorigenesis by stabilizing large tumor suppressor kinase 2 (LATS2) in the Hippo pathway. The Journal of biological chemistry 52 29183995
2015 Alterations in the NF2/LATS1/LATS2/YAP Pathway in Schwannomas. Journal of neuropathology and experimental neurology 52 26360373
2020 LncRNA CRNDE facilitates epigenetic suppression of CELF2 and LATS2 to promote proliferation, migration and chemoresistance in hepatocellular carcinoma. Cell death & disease 51 32826865
2008 Kpm/Lats2 is linked to chemosensitivity of leukemic cells through the stabilization of p73. Blood 51 18565851
2020 O-GlcNAcylation on LATS2 disrupts the Hippo pathway by inhibiting its activity. Proceedings of the National Academy of Sciences of the United States of America 48 32513743
2010 Stability of the LATS2 tumor suppressor gene is regulated by tristetraprolin. The Journal of biological chemistry 46 20335167
2008 LATS2 tumour specific mutations and down-regulation of the gene in non-small cell carcinoma. Lung cancer (Amsterdam, Netherlands) 44 19008013
2014 MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting LATS2. Biochemical and biophysical research communications 42 24735543
2015 miR-107 and miR-25 simultaneously target LATS2 and regulate proliferation and invasion of gastric adenocarcinoma (GAC) cells. Biochemical and biophysical research communications 40 25824045
2020 The Histone Methyltransferase G9a Promotes Cholangiocarcinogenesis Through Regulation of the Hippo Pathway Kinase LATS2 and YAP Signaling Pathway. Hepatology (Baltimore, Md.) 39 31990985
2018 LATS2 promotes apoptosis in non-small cell lung cancer A549 cells via triggering Mff-dependent mitochondrial fission and activating the JNK signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 39 30551520
2016 An evolutionarily conserved negative feedback mechanism in the Hippo pathway reflects functional difference between LATS1 and LATS2. Oncotarget 39 27006470
2019 Long noncoding RNA DDX11-AS1 epigenetically represses LATS2 by interacting with EZH2 and DNMT1 in hepatocellular carcinoma. Biochemical and biophysical research communications 38 31097223
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
2017 The pseudogene DUXAP10 promotes an aggressive phenotype through binding with LSD1 and repressing LATS2 and RRAD in non small cell lung cancer. Oncotarget 38 28029651
2014 Mutation analysis of large tumor suppressor genes LATS1 and LATS2 supports a tumor suppressor role in human cancer. Protein & cell 38 25482410
2013 Lats2 phosphorylates p21/CDKN1A after UV irradiation and regulates apoptosis. Journal of cell science 38 23886938
2019 LINC00511 promotes the progression of non-small cell lung cancer through downregulating LATS2 and KLF2 by binding to EZH2 and LSD1. European review for medical and pharmacological sciences 37 31646568
2015 LATS2-mediated YAP1 phosphorylation is involved in HCC tumorigenesis. International journal of clinical and experimental pathology 34 25973055
2020 Long noncoding RNA NEAT1 suppresses hepatocyte proliferation in fulminant hepatic failure through increased recruitment of EZH2 to the LATS2 promoter region and promotion of H3K27me3 methylation. Experimental & molecular medicine 32 32157157
2018 miR-372 promotes breast cancer cell proliferation by directly targeting LATS2. Experimental and therapeutic medicine 32 29456685
2021 Circular RNA circ_103820 suppresses lung cancer tumorigenesis by sponging miR-200b-3p to release LATS2 and SOCS6. Cell death & disease 31 33589592
2019 Isoliquiritigenin suppresses the proliferation and induced apoptosis via miR-32/LATS2/Wnt in nasopharyngeal carcinoma. European journal of pharmacology 30 31004603
2022 Metallothionein 2A (MT2A) controls cell proliferation and liver metastasis by controlling the MST1/LATS2/YAP1 signaling pathway in colorectal cancer. Cancer cell international 29 35642057
2019 Anti-tumor effect of LATS2 on liver cancer death: Role of DRP1-mediated mitochondrial division and the Wnt/β-catenin pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 29 30981110
2010 A novel Chk1/2-Lats2-14-3-3 signaling pathway regulates P-body formation in response to UV damage. Journal of cell science 29 21118956
2021 The Hippo kinase LATS2 impairs pancreatic β-cell survival in diabetes through the mTORC1-autophagy axis. Nature communications 28 34389720
2019 LATS2 inhibits cell proliferation and metastasis through the Hippo signaling pathway in glioma. Oncology reports 28 30896861
2018 miR-93 Promotes the Growth and Invasion of Prostate Cancer by Upregulating Its Target Genes TGFBR2, ITGB8, and LATS2. Molecular therapy oncolytics 28 30294667
2018 LATS1 and LATS2 suppress breast cancer progression by maintaining cell identity and metabolic state. Life science alliance 28 30456386
2018 miR-650 Promotes the Metastasis and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma by Directly Inhibiting LATS2 Expression. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 28 30481780
2019 MicroRNA-302d promotes the proliferation of human pluripotent stem cell-derived cardiomyocytes by inhibiting LATS2 in the Hippo pathway. Clinical science (London, England : 1979) 25 31239293
2017 Molecular Alterations and Expression Dynamics of LATS1 and LATS2 Genes in Non-Small-Cell Lung Carcinoma. Pathology oncology research : POR 25 28434174
2014 Down-regulation of LATS2 in non-small cell lung cancer promoted the growth and motility of cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 25 25391426
2020 miR-497 regulates fatty acid synthesis via LATS2 in bovine mammary epithelial cells. Food & function 24 32935676
2018 Long non-coding RNA HOTTIP is upregulated in renal cell carcinoma and regulates cell growth and apoptosis by epigenetically silencing of LATS2. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 24 30021349
2019 MiR-135b is a novel oncogenic factor in cutaneous melanoma by targeting LATS2. Melanoma research 23 30480622
2020 MiR-92 overexpression suppresses immune cell function in ovarian cancer via LATS2/YAP1/PD-L1 pathway. Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 22 32654106
2020 Long noncoding RNA HOXA-AS2 functions as an oncogene by binding to EZH2 and suppressing LATS2 in acute myeloid leukemia (AML). Cell death & disease 22 33268767
2015 LATS2 induced by TNF-alpha and inhibited cell proliferation and invasion by phosphorylating YAP in oral squamous cell carcinoma. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 22 25782587
2024 LATS2 condensates organize signalosomes for Hippo pathway signal transduction. Nature chemical biology 21 38200110
2023 Platycodin D confers oxaliplatin Resistance in Colorectal Cancer by activating the LATS2/YAP1 axis of the hippo signaling pathway. Journal of Cancer 21 36860929
2020 The Sp1/FOXC1/HOTTIP/LATS2/YAP/β-catenin cascade promotes malignant and metastatic progression of osteosarcoma. Molecular oncology 21 32634265
2014 Lats2 is critical for the pluripotency and proper differentiation of stem cells. Cell death and differentiation 21 24413153
2009 The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC). Cellular & molecular biology letters 21 19238334
2021 Novel insights into the regulation of LATS2 kinase in prehierarchical follicle development via the Hippo pathway in hen ovary. Poultry science 20 34649058
2019 MiR-372-3p promotes tumor progression by targeting LATS2 in colorectal cancer. European review for medical and pharmacological sciences 20 31646563
2017 The major miR-31 target genes STK40 and LATS2 and their implications in the regulation of keratinocyte growth and hair differentiation. Experimental dermatology 20 28419554
2017 microRNA-605 promotes cell proliferation, migration and invasion in non-small cell lung cancer by directly targeting LATS2. Experimental and therapeutic medicine 20 28673012
2021 MIR22HG inhibits breast cancer progression by stabilizing LATS2 tumor suppressor. Cell death & disease 19 34446703
2019 LATS2 Inhibits Malignant Behaviors of Glioma Cells via Inactivating YAP. Journal of molecular neuroscience : MN 19 30771084

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