Affinage

PLAAT4

Phospholipase A and acyltransferase 4 · UniProt Q9UL19

Length
164 aa
Mass
18.2 kDa
Annotated
2026-04-28
71 papers in source corpus 23 papers cited in narrative 23 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLAAT4 (TIG3/RARRES3/RIG1) is a retinoic acid– and p53-inducible Ca²⁺-independent phospholipase A1/A2 and acyl protein thioesterase that functions as a broad tumor suppressor by attenuating multiple oncogenic signaling cascades and promoting terminal differentiation (PMID:19615464, PMID:25361079, PMID:24867881). Its N-terminal hydrophilic domain harbors catalytic phospholipase activity, while the C-terminal hydrophobic domain directs plasma membrane and Golgi localization, where PLAAT4 directly binds and destabilizes Ras proteins to suppress MAPK signaling, deacylates Wnt ligands and LRP6 to inhibit Wnt/β-catenin signaling, and activates type I transglutaminase during keratinocyte cornified envelope assembly (PMID:20100577, PMID:16005186, PMID:17196792, PMID:25361079, PMID:17762858). PLAAT4 also localizes to the centrosome, where it suppresses centrosome separation and alters microtubule organization, and interacts with RPLP0 and PTGDS to induce cell cycle arrest, apoptosis, and invasion suppression (PMID:22427689, PMID:31131438, PMID:22960220). Transcriptionally, PLAAT4 is directly activated by RAR/RXR via a DR5 promoter element and by p53, and is repressed by BCL6; its phospholipase activity is required for its anti-metastatic and pro-differentiation functions in vivo (PMID:15850806, PMID:22616991, PMID:40777995, PMID:24867881).

Mechanistic history

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

    Establishing that PLAAT4's C-terminal hydrophobic domain is required for membrane targeting and growth suppression resolved how subcellular localization relates to its anti-proliferative function.

    Evidence Truncation mutagenesis with GFP localization and colony formation assays in cultured cells

    PMID:11078805

    Open questions at the time
    • Identity of the membrane compartment was not resolved
    • Catalytic mechanism unknown at this stage
  2. 2005 High

    Identification of the DR5 retinoic acid response element and direct RAR/RXR binding established PLAAT4 as a direct transcriptional target of retinoid signaling, explaining its original discovery as a retinoid-induced gene.

    Evidence Luciferase reporter with promoter deletion/mutation, EMSA with nuclear extracts

    PMID:15850806

    Open questions at the time
    • Other transcription factors regulating PLAAT4 not yet identified
    • Chromatin context of the DR5 element not examined
  3. 2005 High

    Demonstrating that PLAAT4 directly binds Ras and reduces Ras-GTP levels identified Ras as a direct target and placed PLAAT4 upstream of the MAPK cascade.

    Evidence Co-immunoprecipitation, Ras-GTP pull-down, reporter assays with domain mutants

    PMID:16005186

    Open questions at the time
    • Mechanism by which PLAAT4 destabilizes Ras protein not determined
    • Whether enzymatic activity is required for Ras suppression was unknown
  4. 2006 High

    Organelle-targeted constructs pinpointed the Golgi as the critical site for PLAAT4-mediated Ras inhibition and caspase-dependent apoptosis, resolving the spatial requirement for its tumor suppressor activity.

    Evidence Golgi- vs. ER-targeted constructs with caspase activity, MTT/LDH assays

    PMID:17196792

    Open questions at the time
    • Golgi-specific Ras pool regulation mechanism not defined
    • Whether Golgi localization is required for all tumor-suppressive functions unclear
  5. 2007 High

    Mapping the TG1 interaction domain (residues 112–164) and showing that N-terminal removal converts PLAAT4 from a pro-differentiation to a pro-apoptotic factor revealed how domain architecture dictates cell fate choice.

    Evidence Truncation mutant co-precipitation, TG1 substrate assay, cell death assays in keratinocytes

    PMID:17762858 PMID:18612777

    Open questions at the time
    • Structural basis of TG1 activation not solved
    • Whether phospholipase activity contributes to TG1 regulation was untested
  6. 2009 High

    Reconstitution of Ca²⁺-independent phospholipase A1/A2 activity with purified recombinant protein established the intrinsic enzymatic function of PLAAT4, defining it as a lipid-modifying enzyme.

    Evidence In vitro enzymatic assay with purified recombinant protein using PC and PE substrates

    PMID:19615464

    Open questions at the time
    • Physiological lipid substrates in cells not identified
    • Relationship between PLA activity and tumor suppression not established
  7. 2010 High

    Domain dissection showed the N-terminal region (residues 1–134) is sufficient for catalytic PLA2 activity, formally separating catalytic and targeting functions of PLAAT4.

    Evidence Purified domain fragments tested in in vitro phospholipase assay

    PMID:20100577

    Open questions at the time
    • Active-site residues not yet defined by mutagenesis in this study
    • Whether NTD alone has biological activity in cells untested
  8. 2012 High

    Discovery that PLAAT4 localizes to centrosomes and suppresses centrosome separation and microtubule nucleation revealed a cytoskeletal mechanism of growth suppression distinct from signaling pathway inhibition.

    Evidence Co-localization with γ-tubulin/pericentrin, microtubule regrowth assay, tubulin modification western blots, centrosome separation assay

    PMID:21858038 PMID:22427689

    Open questions at the time
    • Molecular target at the centrosome not identified
    • Whether phospholipase activity is required for centrosomal function unknown
  9. 2012 High

    Identification of a functional p53 response element in the PLAAT4 promoter, validated by EMSA and ChIP, established p53 as a second major transcriptional activator alongside retinoid receptors.

    Evidence Luciferase reporter, EMSA, ChIP with wild-type vs. mutant p53

    PMID:22616991

    Open questions at the time
    • Cooperative or independent regulation by p53 and RAR not examined
    • Whether p53-driven PLAAT4 induction is required for p53-dependent apoptosis unknown
  10. 2012 High

    Identifying PTGDS as an interactor that mediates PLAAT4's anti-invasive activity through PGD2/cAMP elevation linked PLAAT4 to prostaglandin metabolism and invasion suppression.

    Evidence Yeast two-hybrid, co-localization, PGD2/cAMP ELISA, siRNA epistasis, migration/invasion assays

    PMID:22960220

    Open questions at the time
    • Whether PLAAT4 enzymatic activity is required for PTGDS activation unknown
    • Interaction not validated by reciprocal Co-IP
  11. 2014 High

    Active-site mutagenesis proved that phospholipase A1/A2 enzymatic activity is required for PLAAT4's pro-differentiation and anti-metastatic functions in vivo, linking catalysis to tumor suppression.

    Evidence Active-site mutant analysis, in vivo breast cancer lung metastasis model

    PMID:24867881

    Open questions at the time
    • Specific lipid products mediating the anti-metastatic effect not identified
    • Whether PLA1 or PLA2 activity is the relevant catalytic mode unclear
  12. 2014 High

    Demonstrating acyl protein thioesterase activity toward Wnt ligands and LRP6 revealed a second enzymatic function — protein deacylation — that suppresses Wnt/β-catenin signaling, EMT, and stemness.

    Evidence Active-site mutagenesis, acylation assays, Wnt/β-catenin reporter, Co-IP

    PMID:25361079

    Open questions at the time
    • Full spectrum of acylated protein substrates unknown
    • Relative contribution of phospholipase vs. thioesterase activity to tumor suppression unresolved
  13. 2015 High

    The solution NMR structure of the N-terminal domain explained why TIG3 NTD enhances rather than inhibits CTD-mediated cell death, providing a structural basis for the functional divergence among PLAAT family members.

    Evidence NMR structure determination, cell death assays with domain constructs

    PMID:25871522

    Open questions at the time
    • Full-length structure not available
    • NTD–CTD intramolecular contacts not resolved in the full-length protein
  14. 2019 High

    Identification of RPLP0 as a physical interactor whose downregulation phenocopies PLAAT4 overexpression established a ribosomal protein–mediated pathway for PLAAT4-induced cell cycle arrest and apoptosis.

    Evidence Yeast two-hybrid, Co-IP, co-localization, parallel siRNA knockdown with viability/apoptosis readouts

    PMID:31131438

    Open questions at the time
    • How PLAAT4 decreases RPLP0 levels (degradation vs. translation) not defined
    • Whether this pathway operates in non-cancer cells unknown
  15. 2021 Medium

    An IFN-γ-stimulated gene screen identified PLAAT4 as a host restriction factor for Toxoplasma gondii, revealing an innate immune function through induction of premature parasite egress.

    Evidence Overexpression screen of 414 ISGs, parasite egress assay in multiple human cell lines

    PMID:34871166

    Open questions at the time
    • Mechanism of egress induction not defined
    • Whether enzymatic activity is required for anti-parasitic function untested
    • Endogenous validation at physiological expression levels lacking
  16. 2025 Medium

    X-ray crystallography of a PLAAT4-derived peptide bound near the Switch II domain of KRAS G12V provided the first atomic-resolution view of PLAAT4–Ras interaction and demonstrated selective cytotoxicity toward KRAS-mutant cells.

    Evidence X-ray crystallography, peptide binding and cell viability assays

    PMID:40752582

    Open questions at the time
    • Peptide-based interaction may not recapitulate full-length protein binding mode
    • In vivo efficacy of peptide not demonstrated
  17. 2025 Medium

    Identification of BCL6 as a transcriptional repressor and CRABP2 as a protein-level destabilizer of PLAAT4 expanded the understanding of upstream regulatory mechanisms controlling PLAAT4 tumor suppressor function.

    Evidence CUT&Tag, RNA-seq, Co-IP, protein stability assays, xenograft models for both studies

    PMID:40657374 PMID:40777995

    Open questions at the time
    • BCL6 binding site in PLAAT4 promoter not mapped to base-pair resolution
    • CRABP2-mediated degradation pathway (proteasomal vs. lysosomal) not defined
    • Both studies from single labs

Open questions

Synthesis pass · forward-looking unresolved questions
  • Major open questions include the identity of specific in vivo lipid substrates, the relative contributions of phospholipase versus thioesterase activities to individual tumor-suppressive functions, and the structural basis of the full-length protein including intramolecular NTD–CTD regulation.
  • Full-length PLAAT4 structure not determined
  • In vivo lipid substrates and acylated protein substrates beyond Wnt/LRP6 not identified
  • Whether centrosomal and Golgi functions require enzymatic activity is unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0008289 lipid binding 2 GO:0098772 molecular function regulator activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005815 microtubule organizing center 3 GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1430728 Metabolism 3 R-HSA-1640170 Cell Cycle 3 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-168256 Immune System 1
Partners
BCL6CRABP2HRASKRASLRP6PTGDSRPLP0TGM1

Evidence

Reading pass · 23 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 PLAAT4 (TIG3/RARRES3) functions as a Ca2+-independent phospholipase A1/A2, hydrolyzing phosphatidylcholines and phosphatidylethanolamines, with PLA1 activity predominating over PLA2 activity; the purified recombinant protein was active in vitro. In vitro enzymatic assay with purified recombinant protein Biochimica et biophysica acta High 19615464
2000 The C-terminal hydrophobic domain of TIG3/PLAAT4 is required for perinuclear/membrane localization and optimal growth suppression; truncation mutants lacking this domain lose membrane targeting and show partial loss of anti-proliferative activity. Truncation mutagenesis, GFP fusion localization, colony formation assay International journal of oncology High 11078805
2005 RIG1/PLAAT4 inhibits Ras/MAPK signaling by suppressing Ras activation (reducing Ras-GTP levels and total Ras protein half-life); co-immunoprecipitation showed direct interaction between RIG1 and Ras protein, and the C-terminal domain of RIG1 is required for this interaction. Co-immunoprecipitation, Ras-GTP pull-down assay, transactivation reporter assay, confocal microscopy Cellular signalling High 16005186
2006 RIG1/PLAAT4 localizes to the ER and Golgi apparatus; Golgi-targeted RIG1 inhibits HRAS activation by >81% and induces apoptosis via caspase-2, -3, and -9 activation, whereas ER-targeted or C-terminal deleted RIG1 is inactive, establishing the Golgi as the critical site for both anti-Ras and pro-apoptotic activities. Confocal microscopy, targeted deletion constructs, caspase activity assays, MTT/LDH assays Cellular signalling High 17196792
2007 The TIG3/PLAAT4 domain spanning amino acids 112–164 is required for interaction with type I transglutaminase (TG1); the N-terminal conserved region is required for keratinocyte differentiation activity, and its removal converts TIG3 into a pro-apoptotic protein associated with membrane redistribution. Truncation mutant co-precipitation, TG1 substrate assay, fluorescence localization, cell death assays The Journal of investigative dermatology High 17762858
2008 TIG3/PLAAT4 interacts with and regulates the activity of type I transglutaminase (TG1) in keratinocytes, representing a novel mechanism for TG1 activation during terminal differentiation. Co-immunoprecipitation, transglutaminase activity assay Amino acids Medium 18612777
2008 RIG1/PLAAT4 downregulates HER2 (p185) and suppresses the PI3K/Akt/mTOR/VEGF signaling pathway in ovarian cancer cells; heregulin specifically restores HER2 and Akt activation suppressed by RIG1. Western blot (phospho-p185, phospho-Akt, mTOR, VEGF), overexpression studies Carcinogenesis Medium 18174256
2009 The NC domain (NC motif, amino acids 112–113) of RIG1/PLAAT4 is the primary determinant of pro-apoptotic activity; NC-motif mutations abolish apoptosis and alter nuclear vs. cytoplasmic localization, while a 12-amino-acid peptide spanning residues 111–123 retains full apoptotic activity in cancer but not normal cells. EGFP-tagged deletion/point mutants, cell death assays, dodecapeptide functional assays BMC cell biology Medium 19245694
2010 The N-terminal hydrophilic region (residues 1–134) of TIG3/PLAAT4 alone is sufficient for Ca2+-independent phospholipase A2 activity, while the hydrophobic C-terminal region is important for cellular localization rather than catalysis. Bacterial expression/purification, in vitro phospholipase activity assay, limited proteolysis Protein expression and purification High 20100577
2011 TIG3/PLAAT4 localizes to the pericentrosomal region in skin cancer cells (SCC-13); this pericentrosomal localization alters microtubule and microfilament organization, drives pericentrosomal organelle clustering (a hallmark of apoptosis), and is associated with reduced cyclins D1/E/A, increased p21, elevated Bax, reduced Bcl-XL, and caspase-3/9/PARP cleavage. Fluorescence microscopy, western blot, co-localization, colony formation/proliferation assays PloS one Medium 21858038
2012 TIG3/PLAAT4 co-localizes with γ-tubulin and pericentrin at the centrosome; centrosomal TIG3 alters microtubule nucleation, reduces anterograde microtubule growth, increases α-tubulin acetylation/detyrosination, promotes a peripheral microtubule ring, and suppresses centrosome separation without affecting duplication, thereby reducing cell proliferation. Co-localization (γ-tubulin, pericentrin markers), microtubule regrowth assay, tubulin modification western blots, centrosome separation assay Journal of cell science High 22427689
2012 RIG1/PLAAT4 gene expression is directly regulated by p53; a functional p53 response element (p53RE) in the RIG1 promoter was identified, and p53 binds this element (demonstrated by EMSA and ChIP), with wild-type but not mutant p53 transactivating the RIG1 promoter. Luciferase reporter assay, site-directed mutation, EMSA, ChIP FEBS letters High 22616991
2012 RIG1/PLAAT4 interacts with prostaglandin D2 synthase (PTGDS), identified by yeast two-hybrid and confirmed by co-localization; in RIG1-expressing testicular cancer cells, PTGDS activity is enhanced, leading to elevated PGD2 and cAMP, which suppresses cell migration and invasion through the PGD2/cAMP/SOX9 pathway. Yeast two-hybrid, co-localization, PGD2/cAMP ELISA, siRNA knockdown, migration/invasion assays Biochimica et biophysica acta High 22960220
2013 The C-terminal hydrophobic domain of TIG3/PLAAT4 targets the protein to the plasma membrane; an N-terminal hydrophilic region segment targets TIG3 to the centrosome; when isolated alone, the C-terminal domain localizes to mitochondria rather than plasma membrane. Domain truncation, GFP-fusion subcellular localization microscopy The Journal of investigative dermatology Medium 24401997
2014 RARRES3/PLAAT4 suppresses breast cancer lung metastasis; its phospholipase A1/A2 enzymatic activity is required for its pro-differentiation function, and loss of RARRES3 facilitates tumor cell adhesion to lung parenchyma. Loss-of-function knockdown, metastasis assays in vivo, active-site mutant analysis EMBO molecular medicine High 24867881
2014 RARRES3/PLAAT4 functions as an acyl protein thioesterase that modulates the acylation status of Wnt proteins and the co-receptor LRP6, thereby suppressing Wnt/β-catenin signaling, EMT, and cancer stem cell properties; mutation of conserved active-site residues abolishes these effects. Active-site mutagenesis, acylation assays, Wnt/β-catenin reporter, co-immunoprecipitation Cell death and differentiation High 25361079
2015 The solution NMR structure of the TIG3/PLAAT4 N-terminal domain reveals overall fold similarity to H-REV107, but the CTD-binding regions on the NTD differ between TIG3 and H-REV107, explaining why TIG3 NTD enhances (while H-REV107 NTD inhibits) CTD-mediated cell death. NMR structure determination, cell death assays with domain constructs FEBS letters High 25871522
2019 PLAAT4 physically interacts with ribosomal protein RPLP0 (identified by yeast two-hybrid, confirmed by co-immunoprecipitation and co-localization); PLAAT4 expression suppresses RPLP0 levels, and both PLAAT4 overexpression and RPLP0 knockdown similarly reduce cell viability, cell cycle-associated proteins, and anti-apoptotic proteins, indicating RPLP0 downregulation mediates PLAAT4-induced cell cycle arrest and apoptosis. Yeast two-hybrid, co-immunoprecipitation, co-localization, siRNA knockdown, cell viability/apoptosis assays Cell biochemistry and biophysics High 31131438
2021 RARRES3/PLAAT4 restricts Toxoplasma gondii infection by inducing premature egress of the parasite from human cells; this was identified through an overexpression screen of 414 IFNγ-induced ISGs. Overexpression screen, parasite egress assay in multiple human cell lines eLife Medium 34871166
2025 A TIG3/PLAAT4-derived peptide binds near the Switch II domain of KRAS G12V, causing conformational changes and reducing viability of KRAS G12V-mutant cancer cell lines; X-ray crystallography revealed the structural basis of the interaction. X-ray crystallography, peptide binding assay, cell viability assay Biochimica et biophysica acta. Proteins and proteomics Medium 40752582
2025 BCL6 transcriptionally represses PLAAT4 in high-grade serous ovarian cancer; PLAAT4 loss downstream of BCL6 activates the PI3K/AKT signaling pathway, promoting tumor cell proliferation, invasion, and migration both in vitro and in vivo. CUT&Tag, RNA-seq, western blot (PI3K-AKT pathway markers), knockdown/overexpression, xenograft model Frontiers in pharmacology Medium 40777995
2025 CRABP2 binds to PLAAT4 protein and decreases its stability; PLAAT4 loss downstream of CRABP2 promotes lipid droplet accumulation and drives NSCLC cell proliferation, migration, invasion, and metastasis. Co-immunoprecipitation, protein stability assay, knockdown rescue experiments, xenograft model, lipid droplet quantification Journal of Cancer Medium 40657374
2005 The retinoic acid response element (DR5 motif at -5243/-5259) in the RIG1/PLAAT4 gene promoter directly binds RAR/RXR heterodimers (confirmed by EMSA with nuclear extracts), and mutation of DR5 abolishes atRA-mediated transcriptional induction. Luciferase reporter assay, deletion/mutation analysis, EMSA Biochemical and biophysical research communications High 15850806

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 Histone methyltransferase G9a promotes liver cancer development by epigenetic silencing of tumor suppressor gene RARRES3. Journal of hepatology 128 28532996
2008 A molecular program for contralateral trajectory: Rig-1 control by LIM homeodomain transcription factors. Neuron 99 18701067
2009 Characterization of the human tumor suppressors TIG3 and HRASLS2 as phospholipid-metabolizing enzymes. Biochimica et biophysica acta 67 19615464
2000 Cloning and characterization of a novel retinoid-inducible gene 1(RIG1) deriving from human gastric cancer cells. Molecular and cellular endocrinology 66 10687848
2014 RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation. EMBO molecular medicine 62 24867881
2009 Double-stranded RNA activates type I interferon secretion in glomerular endothelial cells via retinoic acid-inducible gene (RIG)-1. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 60 19608629
2006 RIG1 suppresses Ras activation and induces cellular apoptosis at the Golgi apparatus. Cellular signalling 48 17196792
2015 Galectins regulate the inflammatory response in airway epithelial cells exposed to microbial neuraminidase by modulating the expression of SOCS1 and RIG1. Molecular immunology 44 26355912
2003 Induction of TIG3, a putative class II tumor suppressor gene, by retinoic acid in head and neck and lung carcinoma cells and its association with suppression of the transformed phenotype. Oncogene 43 12879006
2005 RIG1 inhibits the Ras/mitogen-activated protein kinase pathway by suppressing the activation of Ras. Cellular signalling 42 16005186
2000 The carboxy-terminal hydrophobic domain of TIG3, a class II tumor suppressor protein, is required for appropriate cellular localization and optimal biological activity. International journal of oncology 38 11078805
2017 RIG-1 and MDA-5 signaling pathways contribute to IFN-β production and viral replication in porcine circovirus virus type 2-infected PK-15 cells in vitro. Veterinary microbiology 37 29102119
2008 Downregulation of HER2 by RIG1 involves the PI3K/Akt pathway in ovarian cancer cells. Carcinogenesis 37 18174256
2012 Pathogen recognition in the human female reproductive tract: expression of intracellular cytosolic sensors NOD1, NOD2, RIG-1, and MDA5 and response to HIV-1 and Neisseria gonorrhea. American journal of reproductive immunology (New York, N.Y. : 1989) 34 22984986
2014 RIG-1 receptor expression in the pathology of Alzheimer's disease. Journal of neuroinflammation 31 24694234
2017 Retinoic Acid Inducible Gene 1 Protein (RIG1)-Like Receptor Pathway Is Required for Efficient Nuclear Reprogramming. Stem cells (Dayton, Ohio) 30 28276156
2009 Induction of apoptosis by the retinoid inducible growth regulator RIG1 depends on the NC motif in HtTA cervical cancer cells. BMC cell biology 30 19245694
2007 Localization of the TIG3 transglutaminase interaction domain and demonstration that the amino-terminal region is required for TIG3 function as a keratinocyte differentiation regulator. The Journal of investigative dermatology 30 17762858
2003 RARRES3 expression positively correlated to tumour differentiation in tissues of colorectal adenocarcinoma. British journal of cancer 30 12838316
2001 The class II tumor-suppressor gene RARRES3 is expressed in B cell lymphocytic leukemias and down-regulated with disease progression. Leukemia 29 11587209
2014 TIG3: an important regulator of keratinocyte proliferation and survival. The Journal of investigative dermatology 27 24599174
2015 RARRES3 suppressed metastasis through suppression of MTDH to regulate epithelial-mesenchymal transition in colorectal cancer. American journal of cancer research 26 26269758
2012 Expression of the class II tumor suppressor gene RIG1 is directly regulated by p53 tumor suppressor in cancer cell lines. FEBS letters 26 22616991
2014 Involvement of RARRES3 in the regulation of Wnt proteins acylation and signaling activities in human breast cancer cells. Cell death and differentiation 25 25361079
2019 The Ribosomal Protein RPLP0 Mediates PLAAT4-induced Cell Cycle Arrest and Cell Apoptosis. Cell biochemistry and biophysics 24 31131438
2012 Involvement of the prostaglandin D2 signal pathway in retinoid-inducible gene 1 (RIG1)-mediated suppression of cell invasion in testis cancer cells. Biochimica et biophysica acta 24 22960220
2004 Rig-1 a new member of Robo family genes exhibits distinct pattern of expression during mouse development. Gene expression patterns : GEP 24 14678835
2021 Overexpression screen of interferon-stimulated genes identifies RARRES3 as a restrictor of Toxoplasma gondii infection. eLife 21 34871166
2015 Are RIG-1 and MDA5 Expressions Associated with Chronic HBV Infection? Viral immunology 21 26485346
2011 TIG3 tumor suppressor-dependent organelle redistribution and apoptosis in skin cancer cells. PloS one 21 21858038
2022 Histone H3K36me2 demethylase KDM2A promotes bladder cancer progression through epigenetically silencing RARRES3. Cell death & disease 20 35697678
2017 The metastasis suppressor RARRES3 as an endogenous inhibitor of the immunoproteasome expression in breast cancer cells. Scientific reports 20 28051153
2005 Identification and characterization of the retinoic acid response elements in the human RIG1 gene promoter. Biochemical and biophysical research communications 20 15850806
2008 TIG3: a regulator of type I transglutaminase activity in epidermis. Amino acids 18 18612777
2005 Decreased expression of type II tumor suppressor gene RARRES3 in tissues of hepatocellular carcinoma and cholangiocarcinoma. World journal of gastroenterology 18 15742394
2021 MiR-139 Induces an Interferon-β Response in Prostate Cancer Cells by Binding to RIG-1. Cancer genomics & proteomics 16 33893074
2010 Expression, purification and biochemical characterization of the N-terminal regions of human TIG3 and HRASLS3 proteins. Protein expression and purification 16 20100577
2005 Expression and regulation of retinoid-inducible gene 1 (RIG1) in breast cancer. Anticancer research 16 16080475
2002 Pax-2 interacts with RB and reverses its repression on the promoter of Rig-1, a Robo member. Biochemical and biophysical research communications 15 12200151
2018 Neuronal transcriptomic responses to Japanese encephalitis virus infection with a special focus on chemokine CXCL11 and pattern recognition receptors RIG-1 and MDA5. Virology 14 30481615
2021 Upregulation of HOXC9 generates interferon-gamma resistance in gastric cancer by inhibiting the DAPK1/RIG1/STAT1 axis. Cancer science 13 34159686
2015 Structural and functional characterization of tumor suppressors TIG3 and H-REV107. FEBS letters 13 25871522
2005 Suppression of the TIG3 tumor suppressor gene in human ovarian carcinomas is mediated via mitogen-activated kinase-dependent and -independent mechanisms. International journal of cancer 13 15856468
2023 Rig1 receptor plays a critical role in cardiac reprogramming via YY1 signaling. American journal of physiology. Cell physiology 11 36847443
2017 4(3H)-Quinazolone regulates innate immune signaling upon respiratory syncytial virus infection by moderately inhibiting the RIG-1 pathway in RAW264.7 cell. International immunopharmacology 11 28957692
2017 Systematic prioritization of functional hotspot in RIG-1 domains using pattern based conventional molecular dynamic simulation. Life sciences 10 28705469
2012 TIG3 interaction at the centrosome alters microtubule distribution and centrosome function. Journal of cell science 10 22427689
2022 Simultaneous Detection of RIG-1, MDA5, and IFIT-1 Expression Is a Convenient Tool for Evaluation of the Interferon-Mediated Response. Viruses 9 36298646
2023 The differential expression of toll like receptors and RIG-1 correlates to the severity of infectious diseases. Annals of diagnostic pathology 8 36634551
2021 Innate Immune Responses to Wildtype and Attenuated Sheeppox Virus Mediated Through RIG-1 Sensing in PBMC In-Vitro. Frontiers in immunology 8 34211465
2013 Pericentrosomal localization of the TIG3 tumor suppressor requires an N-terminal hydrophilic region motif. The Journal of investigative dermatology 8 24401997
2023 Japanese encephalitis virus induces apoptosis by activating the RIG-1 signaling pathway. Archives of virology 7 37233865
2017 VS-5584 mediates potent anti-myeloma activity via the upregulation of a class II tumor suppressor gene, RARRES3 and the activation of Bim. Oncotarget 7 29254208
2016 The antitumor effect of TIG3 in liver cancer cells is involved in ERK1/2 inhibition. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 7 26951515
2015 RARRES3 regulates signal transduction through post-translational protein modifications. Molecular & cellular oncology 7 27308522
2014 Insight into buffalo (Bubalus bubalis) RIG1 and MDA5 receptors: a comparative study on dsRNA recognition and in-vitro antiviral response. PloS one 7 24587036
2020 The effect of IFN-β 1a on expression of MDA5 and RIG-1 in multiple sclerosis patients. Biotechnology and applied biochemistry 6 32311159
2012 1H, 13C, and 15N resonance assignments of the N-terminal domain of human TIG3. Biomolecular NMR assignments 6 22290676
2008 Effects of narrow-band ultraviolet B and tazarotene therapy on keratinocyte proliferation and TIG3 expression. The Journal of dermatology 6 19017044
2022 Retinoic acid-inducible gene 1 (RIG-1) and IFN-β promoter stimulator-1 (IPS-1) significantly down-regulated in the severe coronavirus disease 2019 (COVID-19). Molecular biology reports 5 36309611
2019 Peculiarities of RIG-1 Expression in Placental Villi in Preeclampsia. Bulletin of experimental biology and medicine 5 31656003
2022 Interferon-α2b-Induced RARRES3 Upregulation Inhibits Hypertrophic Scar Fibroblasts' Proliferation and Migration Through Wnt/β-Catenin Pathway Suppression. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 4 36520614
2022 The differential expression of toll like receptors and RIG-1 in the placenta of neonates with in utero infections. Annals of diagnostic pathology 2 36535188
2017 Comparison of transcriptional profiles of interferons, CXCL10 and RIG-1 in influenza infected A549 cells stimulated with exogenous interferons. Acta virologica 2 28523924
2013 Lewis lung carcinoma progression is facilitated by TIG-3 fibroblast cells. Anticancer research 2 24023311
2024 MITOCHONDRIAL ANTIVIRAL PATHWAYS CONTROL ANTI-HIV RESPONSES AND ISCHEMIC STROKE OUTCOMES VIA THE RIG-1 SIGNALING AND INNATE IMMUNITY MECHANISMS. bioRxiv : the preprint server for biology 1 38895303
2026 Transcriptomic landscape of transposable elements reveals LTR7-PLAAT4 as a potential oncogene and therapeutic target in pancreatic adenocarcinoma. Genome research 0 41506784
2025 CRABP2 promotes metastasis and lipid droplet accumulation in non-small cell lung cancer by downregulating PLAAT4. Journal of Cancer 0 40657374
2025 Tazarotene-Induced Gene 3 (TIG3) Induces Apoptosis in Melanoma Cells Through the Modulation of Inhibitors of Apoptosis Proteins. Biomedicines 0 40722819
2025 Structural insights of the complex formed by KRAS G12V and a novel TIG3 peptide. Biochimica et biophysica acta. Proteins and proteomics 0 40752582
2025 BCL6 promotes the progression of high-grade serous ovarian cancer cells by inhibiting PLAAT4. Frontiers in pharmacology 0 40777995