Affinage

TFPI2

Tissue factor pathway inhibitor 2 · UniProt P48307

Length
235 aa
Mass
26.9 kDa
Annotated
2026-04-28
100 papers in source corpus 18 papers cited in narrative 18 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TFPI2 is a secreted Kunitz-type serine protease inhibitor that functions as a broad regulator of extracellular proteolysis, hemostasis, innate immunity, and tumor suppression. It directly inhibits trypsin, plasmin, and thrombin, and suppresses MMP-1, MMP-2, and MMP-3 activity through MAPK pathway downregulation, thereby restraining extracellular matrix degradation, cell invasion, and metastasis in multiple cancer types including pancreatic, glioma, breast, and small cell lung cancer (PMID:579296, PMID:4026390, PMID:15592528, PMID:21530612, PMID:23905012, PMID:32248791). Its promoter is frequently silenced in tumors by CpG hypermethylation maintained through diverse epigenetic mechanisms including mono-ADP-ribosylation of H3R117 that blocks TET1-mediated demethylation, and lncRNA-mediated recruitment of EZH2, LSD1, or MBD3-NuRD repressor complexes (PMID:12956419, PMID:30651599, PMID:31186379, PMID:35501390). In glioblastoma, secreted TFPI2 sustains stem cell self-renewal via JNK-STAT3 signaling and engages the receptor CD51 on microglia to drive immunosuppressive STAT6 polarization, while its C-terminal peptide EDC34 exerts direct bactericidal and complement-activating activities (PMID:37067051, PMID:24339780).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1977 Medium

    Identification of PP5/TFPI2 as a placental glycoprotein with serine proteinase inhibitor activity established the foundational biochemistry of the protein, answering what molecular activity it encodes.

    Evidence Immunoadsorbent purification from human placenta with enzymatic inhibition assays against trypsin and plasmin

    PMID:579296

    Open questions at the time
    • Inhibitory mechanism (Kunitz domain involvement) not yet defined
    • No structural characterization
    • Range of protease targets unknown
  2. 1985 Medium

    Demonstration that PP5/TFPI2 inhibits thrombin-induced fibrinogen coagulation expanded its substrate repertoire to the coagulation cascade and clarified that, unlike antithrombin III, heparin does not serve as a cofactor for its activity.

    Evidence In vitro fibrinogen coagulation assay and heparin-binding assay

    PMID:4026390

    Open questions at the time
    • Physiological relevance to hemostasis in vivo not tested
    • Stoichiometry and kinetics of thrombin inhibition undefined
  3. 1998 Medium

    Localization of TFPI2 mRNA specifically to syncytiotrophoblasts across gestation established the cell type responsible for its placental production and noted its loss in choriocarcinoma, foreshadowing its tumor-suppressive role.

    Evidence In situ hybridization and Northern blot on human placental tissue and choriocarcinoma cell lines

    PMID:9548189

    Open questions at the time
    • Mechanism of silencing in choriocarcinoma not addressed
    • Functional role in trophoblast biology not tested
  4. 2003 Medium

    Identification of CpG island promoter hypermethylation as the mechanism silencing TFPI2 in choriocarcinoma cells provided the first epigenetic explanation for its loss in cancer.

    Evidence 5-aza-2'-deoxycytidine demethylation, methylated luciferase reporter constructs, bisulfite sequencing in JAR cells

    PMID:12956419

    Open questions at the time
    • Upstream signals initiating hypermethylation unknown
    • Generalizability to other tumor types not yet shown
  5. 2005 High

    Re-expression of TFPI2 in pancreatic cancer cells suppressed proliferation, migration, and invasion, establishing it as a functional tumor suppressor whose loss enables extracellular matrix degradation.

    Evidence Stable transfection/re-expression with proliferation, migration, invasion assays and methylation-specific PCR in pancreatic cancer cell lines

    PMID:15592528

    Open questions at the time
    • Specific protease targets mediating ECM degradation not identified in this system
    • In vivo tumor suppressor activity not tested
  6. 2011 Medium

    Knockdown of TFPI2 in glioma cells increased proliferation and invasion specifically through enhanced MMP-1 and MMP-2 activity, placing MMP inhibition as the proximal mechanism of its anti-invasive function.

    Evidence Lentiviral shRNA knockdown with MMP inhibitor rescue experiments in glioma cell lines

    PMID:21530612

    Open questions at the time
    • Whether TFPI2 directly inhibits MMP-1/2 or acts indirectly not resolved
    • In vivo relevance in glioma not shown in this study
  7. 2013 Medium

    TFPI2 overexpression in small cell lung cancer cells revealed that it downregulates MMP-1/3 expression by reducing MAPK pathway phosphorylation and suppresses orthotopic tumor growth, establishing a signaling mechanism upstream of MMP transcription.

    Evidence Stable overexpression, Western blot of MAPK phosphorylation, MMP expression analysis, orthotopic mouse model

    PMID:23905012

    Open questions at the time
    • How a secreted protease inhibitor alters intracellular MAPK signaling is unclear
    • Receptor or membrane target mediating this effect not identified
  8. 2013 High

    The C-terminal peptide EDC34 derived from TFPI2 was shown to have direct bactericidal activity, to activate the classical complement pathway generating antimicrobial C3a, and to inhibit bacteria-induced contact activation, revealing an innate immune function distinct from its protease inhibitor activity.

    Evidence In vitro bactericidal assays, complement activation assays, mouse infection models with E. coli and P. aeruginosa

    PMID:24339780

    Open questions at the time
    • Whether full-length TFPI2 shares these antimicrobial properties is unclear
    • Structural basis for complement activation not defined
  9. 2019 High

    Multiple epigenetic silencing mechanisms converging on the TFPI2 promoter were elucidated: mono-ADP-ribosylation of H3R117 maintains promoter hypermethylation by blocking TET1 access, while lncRNAs recruit EZH2, LSD1, and MBD3-NuRD complexes, collectively explaining the diverse routes to TFPI2 loss in cancer.

    Evidence ChIP, bisulfite sequencing, TET1 KO, H3R117A mutation, ATAC-seq (colorectal cancer); RIP/ChIP with functional rescue (glioblastoma, trophoblast, hepatocellular carcinoma)

    PMID:30195776 PMID:30651599 PMID:31186379 PMID:35501390

    Open questions at the time
    • Relative contribution of each epigenetic pathway in specific tumor types not compared
    • Whether these mechanisms operate in normal tissue homeostasis unknown
  10. 2020 Medium

    TFPI2 was found to suppress breast cancer invasion through downregulation of TWIST1 and its downstream target integrin α5, adding an EMT-linked transcriptional axis to its tumor-suppressive repertoire.

    Evidence Overexpression/knockdown in breast cancer cells, in vivo xenograft, Western blot of TWIST1-integrin α5 axis

    PMID:32248791

    Open questions at the time
    • Mechanism by which a secreted protease inhibitor regulates TWIST1 transcription not defined
    • Direct physical interaction not shown
  11. 2022 Medium

    TFPI2 was shown to promote TGF-β2/Smad signaling-driven endothelial-mesenchymal transition in diabetic nephropathy by disrupting the SMURF2-SMAD7 interaction, revealing a context-dependent pro-fibrotic role separate from its tumor-suppressive functions.

    Evidence Co-immunoprecipitation, AAV-mediated shRNA in vivo, overexpression in renal endothelial cells under high glucose

    PMID:35157852

    Open questions at the time
    • Whether this SMURF2-SMAD7 disruption occurs via direct binding or protease activity is unknown
    • Relevance to non-diabetic fibrotic settings not tested
  12. 2023 High

    Identification of CD51 as the microglial receptor for secreted TFPI2 and delineation of dual signaling—JNK-STAT3 in glioblastoma stem cells promoting self-renewal and STAT6 in microglia driving immunosuppression—provided a receptor-to-phenotype mechanism linking TFPI2 to the tumor immune microenvironment.

    Evidence Receptor identification (CD51), co-IP/binding assays, STAT3/STAT6 pathway analysis, mouse GBM models with anti-PD1 combination, flow cytometry

    PMID:37067051

    Open questions at the time
    • Whether CD51 engagement requires full-length TFPI2 or specific domains is unknown
    • Generalizability of TFPI2-CD51-STAT6 axis beyond glioblastoma not tested
    • Structural basis of TFPI2-CD51 interaction not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single secreted Kunitz-type inhibitor exerts such divergent intracellular signaling effects (MAPK, JNK-STAT3, STAT6, TGF-β/Smad) and whether these depend on its protease-inhibitory activity, direct receptor engagement (e.g., CD51), or distinct protein domains remains an open question.
  • Domain-function mapping for signaling versus protease inhibition not performed
  • No structural model of TFPI2 with receptors or substrates
  • Relative importance of autocrine versus paracrine roles in the tumor microenvironment unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0048018 receptor ligand activity 1
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 2 R-HSA-109582 Hemostasis 1
Partners
CD51MMP-1MMP-2SMAD7SMURF2

Evidence

Reading pass · 18 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1977 Placental protein PP5 (later identified as TFPI2) was isolated from human term placenta and characterized as a glycoprotein (MW ~36,600 Da) with serine proteinase-inhibiting activity, capable of inhibiting trypsin and plasmin. Immunoadsorbent purification, ultracentrifugation, electrophoresis, enzymatic inhibition assays Archiv fur Gynakologie Medium 579296
1985 PP5/TFPI2 inhibits thrombin-induced coagulation of fibrinogen in a dose-dependent manner, similar to antithrombin III, but without heparin-cofactor activity; PP5 binds heparin but heparin does not accelerate its inhibitory effect. In vitro fibrinogen coagulation assay, heparin-binding assay Archives of gynecology Medium 4026390
1998 PP5/TFPI2 mRNA is specifically expressed in syncytiotrophoblasts of human placenta at all gestational periods examined, with no or little expression in choriocarcinoma cell lines, indicating syncytiotrophoblasts as the principal production site. In situ hybridization, Northern blot analysis Placenta Medium 9548189
2003 Hypermethylation of the TFPI-2 CpG island promoter silences TFPI-2 transcription in JAR choriocarcinoma cells; in vitro methylation of TFPI-2/luciferase promoter constructs confirmed methylation-dependent transcriptional silencing. 5'-aza-2'-deoxycytidine demethylation, luciferase reporter assay, bisulfite genomic sequencing Biological chemistry Medium 12956419
2005 Restored expression of TFPI-2 in pancreatic cancer cells (which have epigenetically silenced TFPI-2) suppresses proliferation, migration, and invasive potential in vitro, establishing TFPI-2 as a functional tumor suppressor through inhibition of extracellular matrix degradation. Stable transfection/re-expression, proliferation assay, migration assay, invasion assay, methylation-specific PCR, microarray Oncogene High 15592528
2007 A novel aberrantly-spliced TFPI-2 (asTFPI-2) transcript lacking 5'-UTR and poly(A)+ tail is expressed 4- to 50-fold more in tumor cells than normal cells, representing an additional mechanism by which tumor cells downregulate functional TFPI-2 protein to enhance extracellular matrix degradation. RT-PCR, 5'- and 3'-RACE, quantitative real-time RT-PCR, nucleotide sequence analysis Molecular cancer Medium 17352822
2011 Lentiviral knockdown of TFPI-2 in glioma cell lines significantly increased cell proliferation, migration, and invasion; the anti-invasive properties of TFPI-2 were associated with inhibition of MMP-1 and MMP-2 activity. Lentiviral shRNA knockdown, proliferation assay, migration assay, invasion assay, MMP inhibitor experiments Neuroscience letters Medium 21530612
2013 The TFPI-2 derived C-terminal peptide EDC34 exerts direct bactericidal effects, boosts activation of the classical complement pathway including formation of antimicrobial C3a, and inhibits bacteria-induced activation of the contact/coagulation system. In vitro bactericidal assay, complement activation assay, mouse infection models (E. coli, P. aeruginosa) PLoS pathogens High 24339780
2013 TFPI2 is specifically secreted by ovarian clear cell adenocarcinoma (CCA) cell lines and detected at elevated levels in patient sera, identified via mass spectrometry of conditioned media as a biomarker distinguishing CCA from other epithelial ovarian cancer subtypes. Mass spectrometry of conditioned media, RT-PCR, Western blot, ELISA Journal of proteome research Medium 23805888
2018 lncRNA AC003092.1 regulates TFPI-2 expression through miR-195 by acting as a competing endogenous RNA (ceRNA), increasing TFPI-2 levels and promoting TMZ-induced apoptosis in glioblastoma cells. qRT-PCR, ceRNA/miRNA luciferase reporter assay, overexpression/knockdown, in vitro and in vivo functional assays Cell death & disease Medium 30442884
2018 lncRNA linc00473 inhibits TFPI2 transcription in trophoblast cells through binding to LSD1 (lysine-specific demethylase 1), thereby suppressing TFPI2 expression and affecting trophoblast proliferation and apoptosis. RNA-seq, qRT-PCR, RNA immunoprecipitation, siRNA knockdown, overexpression Molecular therapy. Nucleic acids Medium 30195776
2019 lncRNA AGAP2-AS1 interacts with EZH2 and LSD1 and recruits them to the TFPI2 promoter to suppress TFPI2 transcription, promoting glioblastoma cell proliferation and invasion; TFPI2 overexpression reversed AGAP2-AS1-driven oncogenic effects. RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP), overexpression/knockdown, in vitro and in vivo functional assays Aging Medium 31186379
2019 Mono-ADP-ribosylation of histone H3R117 suppresses TET1 expression and reduces TET1 affinity for the TFPI2 promoter (via H3K9me3 enrichment), thereby impairing demethylation and maintaining hypermethylation of the TFPI2 promoter in colorectal cancer cells. Chromatin immunoprecipitation, bisulfite sequencing, TET1 knockout, H3R117A mutation, ATAC-seq, DNA methylation analysis Oncogene High 30651599
2020 TFPI2 suppresses breast cancer cell proliferation, migration, and invasion through inhibiting TWIST1 expression; TWIST1 in turn upregulates integrin α5, and TFPI2 overexpression suppresses tumor growth in vivo via the TWIST1-integrin α5 axis. CCK8 assay, colony formation, wound healing, transwell invasion, Western blot, in vivo xenograft model, immunohistochemistry Molecular medicine (Cambridge, Mass.) Medium 32248791
2022 MBD3 inhibits TFPI2 transcription via the NuRD complex-mediated deacetylation, reactivating MMP activity and PI3K/AKT signaling, thereby promoting hepatocellular carcinoma growth and metastasis. ChIP, immunoprecipitation, siRNA knockdown, overexpression, in vitro and in vivo functional assays, immunohistochemistry British journal of cancer Medium 35501390
2022 TFPI2 promotes TGF-β2/Smad signaling-driven endothelial-mesenchymal transition in diabetic nephropathy by interfering with the interaction between SMURF2 and SMAD7, preventing SMAD7-mediated inhibition of the TGF-β2 pathway. Co-immunoprecipitation, AAV-mediated shRNA knockdown in vivo, overexpression in human renal glomerular endothelial cells, high-glucose treatment, EndMT marker analysis The Journal of biological chemistry Medium 35157852
2023 TFPI2 promotes glioblastoma stem cell (GSC) self-renewal and tumor growth via activation of the JNK-STAT3 pathway; secreted TFPI2 binds CD51 on microglia to trigger immunosuppressive polarization through STAT6 signaling; inhibition of the TFPI2-CD51-STAT6 axis activates T cells and synergizes with anti-PD1 therapy. Receptor identification (CD51), co-immunoprecipitation/binding assays, genetic knockdown/overexpression, STAT3/STAT6 pathway analysis, mouse GBM models with anti-PD1 combination, flow cytometry Nature immunology High 37067051
2013 TFPI-2 overexpression in small cell lung cancer cells decreased MMP expression (particularly MMP-1 and MMP-3) by downregulating phosphorylation of MAPK signaling pathway proteins, and inhibited tumor growth in an orthotopic mouse model. Stable overexpression, in vitro viability/apoptosis/cell cycle assays, MMP expression analysis, Western blot (MAPK phosphorylation), orthotopic mouse model FEBS open bio Medium 23905012

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Contributions of protein phosphatases PP1, PP2A, PP2B and PP5 to the regulation of tau phosphorylation. The European journal of neuroscience 616 16262633
1992 Identification and characterization of Ref-1, a nuclear protein that facilitates AP-1 DNA-binding activity. The EMBO journal 613 1537340
2000 Going APE over ref-1. Mutation research 478 11018583
1997 Identification of redox/repair protein Ref-1 as a potent activator of p53. Genes & development 423 9119221
1994 The redox and DNA-repair activities of Ref-1 are encoded by nonoverlapping domains. Proceedings of the National Academy of Sciences of the United States of America 326 7506414
2004 Retrovirus resistance factors Ref1 and Lv1 are species-specific variants of TRIM5alpha. Proceedings of the National Academy of Sciences of the United States of America 319 15249685
2004 The human and African green monkey TRIM5alpha genes encode Ref1 and Lv1 retroviral restriction factor activities. Proceedings of the National Academy of Sciences of the United States of America 291 15249687
1993 Identification of residues in the human DNA repair enzyme HAP1 (Ref-1) that are essential for redox regulation of Jun DNA binding. Molecular and cellular biology 250 8355688
2001 Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress. The EMBO journal 249 11689443
2005 A vital role for Ape1/Ref1 protein in repairing spontaneous DNA damage in human cells. Molecular cell 234 15694346
2002 Selenomethionine regulation of p53 by a ref1-dependent redox mechanism. Proceedings of the National Academy of Sciences of the United States of America 215 12357032
2003 Restriction of multiple divergent retroviruses by Lv1 and Ref1. The EMBO journal 204 12554640
1999 Ref-1 regulates the transactivation and pro-apoptotic functions of p53 in vivo. The EMBO journal 201 10523305
2009 Methylation of TFPI2 in stool DNA: a potential novel biomarker for the detection of colorectal cancer. Cancer research 197 19435926
2005 Epigenetic inactivation of TFPI-2 as a common mechanism associated with growth and invasion of pancreatic ductal adenocarcinoma. Oncogene 136 15592528
1994 A redox factor protein, ref1, is involved in negative gene regulation by extracellular calcium. The Journal of biological chemistry 121 7961715
1999 Ser/Thr protein phosphatase type 5 (PP5) is a negative regulator of glucocorticoid receptor-mediated growth arrest. Biochemistry 108 10413457
1977 [Isolation and characterization of the placental protein pp5 (author's transl)]. Archiv fur Gynakologie 96 579296
2012 RNA ligase RtcB splices 3'-phosphate and 5'-OH ends via covalent RtcB-(histidinyl)-GMP and polynucleotide-(3')pp(5')G intermediates. Proceedings of the National Academy of Sciences of the United States of America 93 22474365
2024 Peptide REF1 is a local wound signal promoting plant regeneration. Cell 87 38781969
1998 Levels of the DNA repair enzyme human apurinic/apyrimidinic endonuclease (APE1, APEX, Ref-1) are associated with the intrinsic radiosensitivity of cervical cancers. British journal of cancer 85 9820167
2005 Restriction of feline immunodeficiency virus by Ref1, Lv1, and primate TRIM5alpha proteins. Journal of virology 84 16306589
2005 Analysis of nuclear transport signals in the human apurinic/apyrimidinic endonuclease (APE1/Ref1). Nucleic acids research 80 15942031
1998 Ref-1 controls pax-8 DNA-binding activity. Biochemical and biophysical research communications 80 9813166
2001 Overexpression of Ref-1 inhibits hypoxia and tumor necrosis factor-induced endothelial cell apoptosis through nuclear factor-kappab-independent and -dependent pathways. Circulation research 79 11420300
2009 Estrogen inhibits glucocorticoid action via protein phosphatase 5 (PP5)-mediated glucocorticoid receptor dephosphorylation. The Journal of biological chemistry 75 19586900
2016 Acute exercise stress promotes Ref1/Nrf2 signalling and increases mitochondrial antioxidant activity in skeletal muscle. Experimental physiology 73 26682532
2008 The role of serine/threonine protein phosphatase type 5 (PP5) in the regulation of stress-induced signaling networks and cancer. Cancer metastasis reviews 68 18253812
2003 As(2)O(3) enhances retroviral reverse transcription and counteracts Ref1 antiviral activity. Journal of virology 68 12584341
2012 The Kelch repeat protein KLHDC10 regulates oxidative stress-induced ASK1 activation by suppressing PP5. Molecular cell 67 23102700
2011 Detection of TFPI2 methylation in the serum of colorectal cancer patients. Cancer letters 67 21820798
1997 The serine/threonine phosphatase PP5 interacts with CDC16 and CDC27, two tetratricopeptide repeat-containing subunits of the anaphase-promoting complex. The Journal of biological chemistry 67 9405394
2018 Long noncoding RNA AC003092.1 promotes temozolomide chemosensitivity through miR-195/TFPI-2 signaling modulation in glioblastoma. Cell death & disease 62 30442884
2001 Serine/threonine protein phosphatase 5 (PP5) participates in the regulation of glucocorticoid receptor nucleocytoplasmic shuttling. BMC cell biology 60 11389770
2006 Selenium protection from DNA damage involves a Ref1/p53/Brca1 protein complex. Anticancer research 59 16619485
2019 Long non-coding RNA AGAP2-AS1 exerts oncogenic properties in glioblastoma by epigenetically silencing TFPI2 through EZH2 and LSD1. Aging 56 31186379
1998 Specific expression of PP5/TFPI2 mRNA by syncytiotrophoblasts in human placenta as revealed by in situ hybridization. Placenta 56 9548189
2023 Kunitz-type protease inhibitor TFPI2 remodels stemness and immunosuppressive tumor microenvironment in glioblastoma. Nature immunology 54 37667051
2008 Elevated levels of Ser/Thr protein phosphatase 5 (PP5) in human breast cancer. Biochimica et biophysica acta 51 18280813
2009 Methylation of CLDN6, FBN2, RBP1, RBP4, TFPI2, and TMEFF2 in esophageal squamous cell carcinoma. Oncology reports 49 19288010
2001 Identification of an estrogen-inducible phosphatase (PP5) that converts MCF-7 human breast carcinoma cells into an estrogen-independent phenotype when expressed constitutively. The Journal of biological chemistry 49 11331294
2012 Detection of TFPI2 methylation in the serum of hepatocellular carcinoma patients. Digestive diseases and sciences 47 23108564
2015 Hypermethylation of ITGA4, TFPI2 and VIMENTIN promoters is increased in inflamed colon tissue: putative risk markers for colitis-associated cancer. Journal of cancer research and clinical oncology 46 25902909
2007 Notch-GATA synergy promotes endoderm-specific expression of ref-1 in C. elegans. Development (Cambridge, England) 44 18003741
2022 HSP90-CDC37-PP5 forms a structural platform for kinase dephosphorylation. Nature communications 43 36446791
2010 TFPI-2 is a putative tumor suppressor gene frequently inactivated by promoter hypermethylation in nasopharyngeal carcinoma. BMC cancer 43 21062455
2012 Methylation of TFPI-2 is an early event of esophageal carcinogenesis. Epigenomics 41 22449186
2011 Detection of TFPI2 methylation in the serum of gastric cancer patients. Anticancer research 40 22110206
2007 Redox activation of Ref-1 potentiates cell survival following myocardial ischemia reperfusion injury. Free radical biology & medicine 40 17602955
2005 Capsid processing requirements for abrogation of Fv1 and Ref1 restriction. Journal of virology 40 16051849
2013 Secretome-based identification of TFPI2, a novel serum biomarker for detection of ovarian clear cell adenocarcinoma. Journal of proteome research 39 23805888
2013 The TFPI-2 derived peptide EDC34 improves outcome of gram-negative sepsis. PLoS pathogens 39 24339780
2010 Epigenetic inactivation of the placentally imprinted tumor suppressor gene TFPI2 in prostate carcinoma. Cancer genomics & proteomics 39 20335518
2010 Cervical dysplasia: assessing methylation status (Methylight) of CCNA1, DAPK1, HS3ST2, PAX1 and TFPI2 to improve diagnostic accuracy. Gynecologic oncology 39 20708786
2010 Tissue factor pathway inhibitor 2 (TFPI2) is frequently silenced by aberrant promoter hypermethylation in gastric cancer. Cancer genetics and cytogenetics 38 20113832
2021 SDC2 and TFPI2 Methylation in Stool Samples as an Integrated Biomarker for Early Detection of Colorectal Cancer. Cancer management and research 37 33958894
2018 Long Noncoding RNA 00473 Is Involved in Preeclampsia by LSD1 Binding-Regulated TFPI2 Transcription in Trophoblast Cells. Molecular therapy. Nucleic acids 37 30195776
2006 Rac GTPase signaling through the PP5 protein phosphatase. Proceedings of the National Academy of Sciences of the United States of America 37 16549782
2017 Celastrol ameliorates Cd-induced neuronal apoptosis by targeting NOX2-derived ROS-dependent PP5-JNK signaling pathway. Journal of neurochemistry 36 28129433
2013 The molecular chaperone Hsp70 activates protein phosphatase 5 (PP5) by binding the tetratricopeptide repeat (TPR) domain. The Journal of biological chemistry 36 24327656
2010 Methylation of TFPI2 gene is frequently detected in advanced well-differentiated colorectal cancer. Anticancer research 36 20530429
2023 Hsp90 provides a platform for kinase dephosphorylation by PP5. Nature communications 35 37069154
2020 Metformin attenuates cadmium-induced neuronal apoptosis in vitro via blocking ROS-dependent PP5/AMPK-JNK signaling pathway. Neuropharmacology 35 32209321
2019 P53 supports endothelial barrier function via APE1/Ref1 suppression. Immunobiology 35 31023490
2017 The role of TFPI2 hypermethylation in the detection of gastric and colorectal cancer. Oncotarget 35 29137404
2001 A novel tetratricopeptide repeat (TPR) containing PP5 serine/threonine protein phosphatase in the malaria parasite, Plasmodium falciparum. BMC microbiology 35 11737864
2020 TFPI2 and NDRG4 gene promoter methylation analysis in peripheral blood mononuclear cells are novel epigenetic noninvasive biomarkers for colorectal cancer diagnosis. The journal of gene medicine 34 32196834
2017 Is methylation analysis of SFRP2, TFPI2, NDRG4, and BMP3 promoters suitable for colorectal cancer screening in the Korean population? Intestinal research 33 29142517
2011 Knockdown of TFPI-2 promotes migration and invasion of glioma cells. Neuroscience letters 33 21530612
2004 Selection for loss of Ref1 activity in human cells releases human immunodeficiency virus type 1 from cyclophilin A dependence during infection. Journal of virology 33 15479848
2021 Activation of NRF2 by APE1/REF1 is redox-dependent in Barrett's related esophageal adenocarcinoma cells. Redox biology 30 33887608
2004 Constitutive over expression of serine/threonine protein phosphatase 5 (PP5) augments estrogen-dependent tumor growth in mice. Cancer letters 30 15374638
2014 Epigenetic silencing of TFPI-2 in canine diffuse large B-cell lymphoma. PloS one 28 24695110
2003 Transcriptional silencing of the TFPI-2 gene by promoter hypermethylation in choriocarcinoma cells. Biological chemistry 28 12956419
1999 Microcystin affinity purification of plant protein phosphatases: PP1C, PP5 and a regulatory A-subunit of PP2A. FEBS letters 27 10471836
2007 Complex determinants within the Moloney murine leukemia virus capsid modulate susceptibility of the virus to Fv1 and Ref1-mediated restriction. Virology 26 17343889
1981 Ectopic production of placenta-"specific" tissue proteins (PP5 and PP11) by malignant breast tumors. Archives of gynecology 26 7036917
2013 Protein phosphatase complex PP5/PPP2R3C dephosphorylates P-glycoprotein/ABCB1 and down-regulates the expression and function. Cancer letters 25 24333728
2006 Inhibition of PP2A, but not PP5, mediates p53 activation by low levels of okadaic acid in rat liver epithelial cells. Journal of cellular biochemistry 25 16598789
2020 TFPI2 suppresses breast cancer progression through inhibiting TWIST-integrin α5 pathway. Molecular medicine (Cambridge, Mass.) 24 32248791
2020 Glucocorticoid receptor complexes form cooperatively with the Hsp90 co-chaperones Pp5 and FKBPs. Scientific reports 23 32612187
1981 Detection of placental protein five (PP5) and pregnancy-specific glycoprotein (SP1) in benign and malignant breast disease. Oncodevelopmental biology and medicine : the journal of the International Society for Oncodevelopmental Biology and Medicine 23 6975467
2022 MBD3 promotes hepatocellular carcinoma progression and metastasis through negative regulation of tumour suppressor TFPI2. British journal of cancer 22 35501390
2019 Vitexin ameliorates preeclampsia phenotypes by inhibiting TFPI-2 and HIF-1α/VEGF in a l-NAME induced rat model. Drug development research 22 31486114
2003 Characterization of Saccharomyces cerevisiae protein Ser/Thr phosphatase T1 and comparison to its mammalian homolog PP5. BMC cell biology 22 12694636
1995 Ref-1 expression in adult mammalian neurons and astrocytes. Neuroscience letters 22 7644143
1984 Hyperstimulated human preovulatory follicular fluid contains placental protein 5 (PP5). Fertility and sterility 22 6420205
2022 TFPI2 suppresses the interaction of TGF-β2 pathway regulators to promote endothelial-mesenchymal transition in diabetic nephropathy. The Journal of biological chemistry 21 35157852
2013 Beneficial role of overexpression of TFPI-2 on tumour progression in human small cell lung cancer. FEBS open bio 21 23905012
2021 Exploring transcriptional regulators Ref-1 and STAT3 as therapeutic targets in malignant peripheral nerve sheath tumours. British journal of cancer 20 33658640
2019 Drosophila Ref1/ALYREF regulates transcription and toxicity associated with ALS/FTD disease etiologies. Acta neuropathologica communications 20 31036086
2015 Hypermethylation of TFPI2 correlates with cervical cancer incidence in the Uygur and Han populations of Xinjiang, China. International journal of clinical and experimental pathology 20 25973077
2013 Angiopoietin2 enhances doxorubin resistance in HepG2 cells by upregulating survivin and Ref-1 via MSK1 activation. Cancer letters 20 23643942
2010 Delivery of TFPI-2 using ultrasound with a microbubble agent (SonoVue) inhibits intimal hyperplasia after balloon injury in a rabbit carotid artery model. Ultrasound in medicine & biology 20 20888684
2009 HIF-1 attenuates Ref-1 expression in endothelial cells: reversal by siRNA and inhibition of geranylgeranylation. Vascular pharmacology 20 19524065
2007 Identification of a human TFPI-2 splice variant that is upregulated in human tumor tissues. Molecular cancer 20 17352822
1985 Placental protein 5 (PP5) inhibits thrombin-induced coagulation of fibrinogen. Archives of gynecology 20 4026390
2019 Mono-ADP-ribosylation of H3R117 traps 5mC hydroxylase TET1 to impair demethylation of tumor suppressor gene TFPI2. Oncogene 19 30651599
2016 Rubber particle proteins REF1 and SRPP1 interact differently with native lipids extracted from Hevea brasiliensis latex. Biochimica et biophysica acta. Biomembranes 19 27871841
2012 Effect of acupuncture on hippocampal Ref-1 expression in cerebral multi-infarction rats. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology 19 22391677