Affinage

PROX1

Prospero homeobox protein 1 · UniProt Q92786

Length
737 aa
Mass
83.2 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 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

PROX1 is a homeodomain transcription factor that functions as a master regulator of cell-fate specification across multiple tissues, acting as a binary switch that both activates lineage-defining gene programs and represses alternative-fate genes (PMID:12412020, PMID:19056883). In the lymphatic system it is necessary and sufficient to reprogram blood vascular endothelium toward lymphatic identity, and continuous PROX1 activity is required to maintain that identity—its loss reprograms lymphatic endothelial cells back to a blood vascular phenotype (PMID:12412020, PMID:19056883). PROX1 drives this fate by directly activating lymphatic target genes including FGFR-3, VEGFR3, and podoplanin through binding to defined cis-elements in their promoters (PMID:16291864, PMID:25274728, PMID:24944097), with VEGFR3 establishing a feedback loop in which VEGFC/VEGFR3 signaling sustains PROX1 expression to set lymphatic progenitor number (PMID:25274728). Its DNA-binding specificity and activator-versus-repressor output depend on partner proteins and the responsive element: it heterodimerizes with COUP-TFII/NR2F2 to induce lymphatic genes and block venous Notch-target activation (PMID:18815287, PMID:23345397), cooperates with FOXC2 and Wnt/β-catenin–TCF7L1 to direct valve morphogenesis and lymphatic specification (PMID:22306086, PMID:30332639, PMID:37555328), and assembles its own transcription via a GATA2/FOXC2/NFATC1/PROX1 autoregulatory enhancer (PMID:36697821). Beyond the vasculature, PROX1 controls cell-cycle exit and fate in lens, retina, dentate gyrus neurons, spinal interneurons, hepatoblasts, and slow muscle fibers, frequently by repressing pro-proliferative or alternative-fate genes such as Notch1 and Olig2 at their promoters (PMID:10080188, PMID:12692551, PMID:20808958, PMID:21203589, PMID:24449835, PMID:27731315, PMID:25411508). In metabolic tissues PROX1 acts predominantly as a corepressor, partnering with ERRα/PGC-1α, the LSD1/NuRD complex, and HDAC3 to control energy homeostasis, bile-acid feedback, lipid homeostasis, and rhythmic metabolic outputs (PMID:20194433, PMID:23626788, PMID:21731503, PMID:28916805). PROX1 activity is set post-translationally by SUMOylation at K556, which promotes DNA binding and transcriptional activity (PMID:19706680), and by AMPK-driven phosphorylation at Ser79 that recruits CUL4-DDB1 to trigger ubiquitination and degradation (PMID:36433955); its levels are further tuned post-transcriptionally by miR-181a and the RNA-binding protein CELF1 acting through its 3' UTR (PMID:20558617, PMID:32594240), and transcriptionally by HIF-1α/HIF-2α, SOX18, and YAP/TAZ (PMID:26939885, PMID:30582452, PMID:23395615, PMID:33060128). In cancer, PROX1 promotes hepatocellular and breast tumor progression through Wnt/β-catenin activation and HIF-1α stabilization (PMID:23505027, PMID:25684142, PMID:35342346).

Mechanistic history

Synthesis pass · year-by-year structured walk · 43 steps
  1. 1999 High

    Established the first in vivo developmental role of Prox1, showing it couples cell-cycle exit to terminal differentiation rather than acting merely as a fate marker.

    Evidence Prox1 knockout mouse with lens phenotyping and cell-cycle inhibitor expression analysis

    PMID:10080188

    Open questions at the time
    • Direct transcriptional targets at the lens not defined
    • Mechanism of Cdkn1b/Cdkn1c regulation not resolved
  2. 2001 Medium

    Defined Prox1 as a sequence-specific transcription factor at the gamma-crystallin promoter, mapping its response element and revealing antagonism with Six3.

    Evidence Reporter assays with mapped Prox1- and Six3-responsive promoter elements

    PMID:11139622

    Open questions at the time
    • Direct binding not shown by footprinting/ChIP in this study
    • Mechanism of Six3 antagonism unresolved
  3. 2002 High

    Demonstrated that Prox1 is both necessary and sufficient for lymphatic endothelial cell fate, identifying it as a master switch reprogramming blood vascular toward lymphatic identity.

    Evidence Ectopic expression in human BVECs plus Prox1 knockout mice with transcriptional profiling

    PMID:12412020

    Open questions at the time
    • Direct vs. indirect target genes not distinguished
    • Cofactor requirements not identified
  4. 2003 High

    Generalized Prox1's fate-switch logic to the retina, showing reciprocal control of progenitor cell-cycle exit and horizontal cell identity.

    Evidence Reciprocal knockout and ectopic misexpression in retinal progenitors

    PMID:12692551

    Open questions at the time
    • Direct target genes in retina not identified
    • Molecular mechanism of cell-cycle exit not defined
  5. 2005 Medium

    Identified the first direct lymphatic target gene, FGFR-3, anchoring Prox1's fate-switch to defined cis-regulatory binding.

    Evidence Promoter binding and reporter assays following ectopic Prox1 in BVECs

    PMID:16291864

    Open questions at the time
    • In vivo requirement of FGFR-3 element not tested
    • Single lab
  6. 2008 Medium

    Revealed that Prox1 acts through obligate partnership with COUP-TFII to maintain lymphatic identity, moving the model from a solo switch to a combinatorial code.

    Evidence Reciprocal Co-IP and knockdown co-regulation analysis in LECs

    PMID:18815287

    Open questions at the time
    • Structural basis of heterodimer not defined
    • Genome-wide co-occupancy not yet mapped
  7. 2008 Medium

    Extended Prox1's transcriptional logic to context-dependent activation versus repression, showing output depends on the responsive DNA element in lens crystallin genes.

    Evidence DNase I footprinting, ChIP, and reporter assays across lens cell types and transgenic mice

    PMID:18385074

    Open questions at the time
    • Cofactors distinguishing activation from repression not identified
  8. 2008 High

    Showed Prox1 directly transcribes sarcomeric structural genes, establishing a tissue-specific role in cardiac muscle architecture.

    Evidence Cardiac-specific conditional knockout with transcriptomics and direct regulation assays

    PMID:19091769

    Open questions at the time
    • Cofactors for cardiac targets not identified
  9. 2008 Medium

    Demonstrated Prox1 represses Gfi1 and antagonizes hair-cell fate, broadening its repressor role in inner ear development.

    Evidence Adenoviral transduction in cochlear explants and luciferase repression assays

    PMID:18652815

    Open questions at the time
    • Direct binding to Gfi1 locus not shown
    • In vivo requirement not tested
  10. 2008 High

    Showed continuous Prox1 activity is required to maintain LEC identity even in adults, establishing fate maintenance as an active, cell-autonomous process.

    Evidence Temporally staged conditional knockouts and siRNA knockdown in cultured LECs

    PMID:19056883

    Open questions at the time
    • Upstream signals sustaining Prox1 not defined in this study
  11. 2009 High

    Identified SUMOylation at K556 as a positive post-translational regulator controlling Prox1 DNA binding and lymphatic gene induction.

    Evidence In vitro/in vivo sumoylation assays, K556R mutagenesis, SENP2 reversal, reporter assays

    PMID:19706680

    Open questions at the time
    • SUMO E3 ligase not identified
    • In vivo physiological importance not tested
  12. 2009 Medium

    Defined Prox1 as a promoter-specific corepressor of viral transcription in hepatocytes via LRH-1 and HNF1, illustrating context-dependent repression in the liver.

    Evidence HBV promoter reporter assays, Co-IP for HNF1, and replication assays

    PMID:19264593

    Open questions at the time
    • Direct promoter binding not demonstrated
    • Single lab
  13. 2010 High

    Placed Prox1 at the center of energy homeostasis as a corepressor of the ERRα/PGC-1α metabolic transcriptional network.

    Evidence Co-IP, genome-wide ChIP, reporter assays, and respiratory-capacity measurements in liver cells

    PMID:20194433

    Open questions at the time
    • Mechanism of ERRα/PGC-1α inhibition not resolved at structural level
  14. 2010 High

    Identified miR-181a as a direct post-transcriptional repressor of Prox1 that tunes the lymphatic-versus-blood vascular balance.

    Evidence 3' UTR luciferase reporter and reciprocal miR-181a gain/loss-of-function in primary endothelial cells

    PMID:20558617

    Open questions at the time
    • Upstream control of miR-181a not defined
  15. 2010 High

    Extended Prox1's neurogenic role, showing it drives granule-cell maturation and maintains adult neural progenitors through a non-cell-autonomous feedback loop.

    Evidence Conditional knockout, BrdU labeling, and ectopic expression in the dentate gyrus

    PMID:20808958

    Open questions at the time
    • Molecular nature of the feedback signal not identified
  16. 2011 Medium

    Mechanistically linked Prox1 gene dosage to lymphovenous valve formation through COUP-TFII/Prox1 complex abundance.

    Evidence Prox1 heterozygous mouse analysis with complex formation assays

    PMID:22012621

    Open questions at the time
    • Quantitative threshold of complex required not defined
  17. 2011 Medium

    Integrated Prox1 into circadian-metabolic transcriptional loops via genome-wide co-occupancy with ERRα and BMAL1 in liver.

    Evidence ChIP-seq of ERRα/PROX1/BMAL1 and ERRα-null mouse phenotyping

    PMID:21731503

    Open questions at the time
    • Direct physical interaction with BMAL1 not shown
    • Single lab
  18. 2012 High

    Showed PROX1 cooperates with FOXC2 and fluid shear to translate mechanical signals into lymphatic valve patterning through connexin37 and calcineurin/NFAT.

    Evidence Conditional knockouts, in vitro shear-stress assays, and downstream effector loss-of-function

    PMID:22306086

    Open questions at the time
    • How shear is sensed upstream of the PROX1/FOXC2 module not resolved
  19. 2013 Medium

    Revealed that COUP-TFII/PROX1 heterodimer formation, versus COUP-TFII homodimers, switches endothelial output between lymphatic and venous (Notch-target) programs.

    Evidence Heterodimerization and promoter binding studies with knockdown in endothelial cells

    PMID:23345397

    Open questions at the time
    • Structural basis of the dimer switch not defined
  20. 2013 Medium

    Established HIF-1α/HIF-2α as direct hypoxia-driven activators of Prox1 transcription, linking oxygen sensing to lymphatic fate.

    Evidence EMSA, ChIP, HIF overexpression/knockdown, and Prox1 promoter reporters

    PMID:23395615

    Open questions at the time
    • In vivo physiological relevance of the HRE not tested
  21. 2013 High

    Defined a corepressor mechanism in bile-acid metabolism whereby PROX1 recruits LSD1/NuRD to demethylate and deacetylate the CYP7A1 promoter.

    Evidence IP-MS, GST pulldown, sequential ChIP, and reporter assays

    PMID:23626788

    Open questions at the time
    • Recruitment signal directing PROX1 to CYP7A1 not defined
  22. 2013 Medium

    Implicated PROX1 in hepatocellular carcinoma metastasis through HDAC1-dependent HIF-1α stabilization and EMT, identifying an oncogenic role.

    Evidence Knockdown/overexpression in HCC cells, invasion assays, nude mouse metastasis, and HDAC1 Co-IP

    PMID:23505027

    Open questions at the time
    • Direct HIF-1α deacetylation by recruited HDAC1 not biochemically resolved
  23. 2014 High

    Established a PROX1–VEGFR3 feedback loop as the principal sensing mechanism setting LEC progenitor number, with PROX1 directly and dosage-dependently regulating Vegfr3.

    Evidence Multiple mouse genetic models, ChIP, and VEGFC/VEGFR3 pathway manipulation

    PMID:25274728

    Open questions at the time
    • How VEGFR3 signaling feeds back to the Prox1 promoter not fully traced
  24. 2014 High

    Defined Prox1 as a fate-allocation regulator in liver precursors, promoting hepatocyte over cholangiocyte commitment.

    Evidence Conditional knockout in hepatoblasts with gene expression and morphology analysis

    PMID:24449835

    Open questions at the time
    • Direct hepatocyte target genes not catalogued
  25. 2014 Medium

    Confirmed podoplanin as a direct PROX1 transcriptional target in LECs, extending the catalogue of directly bound lymphatic effector genes.

    Evidence ChIP, DNA pulldown, and luciferase reporter assays in LECs

    PMID:24944097

    Open questions at the time
    • In vivo enhancer requirement not tested
  26. 2014 High

    Showed Prox1 directly represses Olig2 at its promoter and enhancer to specify motor-neuron versus V2 interneuron identity in the spinal cord.

    Evidence In vivo ChIP plus reciprocal gain/loss-of-function in mouse and chick neural tube

    PMID:25411508

    Open questions at the time
    • Cofactors at the Olig2 locus not identified
  27. 2015 High

    Defined Prox1 as a regulator of slow muscle fiber identity through NFAT activation and Notch1 crosstalk.

    Evidence Satellite-cell conditional knockout, gain-of-function, lineage tracing, and NFAT reporters

    PMID:27731315

    Open questions at the time
    • Direct muscle fiber-type target genes not mapped
  28. 2015 Medium

    Showed PROX1 promotes HCC proliferation by transactivating the β-catenin promoter and enhancing nuclear β-catenin, defining an oncogenic Wnt-activating mechanism.

    Evidence Knockdown/overexpression, β-catenin promoter reporter, nuclear fractionation, and xenografts

    PMID:25684142

    Open questions at the time
    • Direct binding of PROX1 to the β-catenin promoter not shown
  29. 2016 High

    Resolved the structural and functional basis of SOX18 binding to the Prox1 regulatory DNA element, defining an upstream transcriptional input.

    Evidence 1.75Å crystal structure, DNA binding assays, and decoy oligonucleotide reporter inhibition

    PMID:26939885

    Open questions at the time
    • In vivo contribution of this element to Prox1 expression not tested here
  30. 2017 High

    Identified an in vivo HDAC3–PROX1 corepressor module recruited by HNF4α that controls hepatic lipid homeostasis.

    Evidence Cross-linking MS, ChIP-seq co-occupancy, and conditional knockouts with metabolic phenotyping

    PMID:28916805

    Open questions at the time
    • Stoichiometry and assembly order of the HDAC3-PROX1 module not defined
  31. 2018 Medium

    Showed PROX1 partners with β-catenin/TCF7L1 to act as a Wnt signaling component driving FOXC2/GATA2 expression in LECs.

    Evidence Co-IP, reporter assays, LEC-specific Wntless knockout, and shear-stress assays

    PMID:30332639

    Open questions at the time
    • Direct vs. cofactor-mediated DNA binding within the complex not resolved
  32. 2018 Medium

    Defined PROX1 repression of MMP14 as a brake on invasive/angiogenic behavior, linking it to extracellular matrix remodeling.

    Evidence Conditional knockout, siRNA knockdown, promoter binding, and 3D invasion assays

    PMID:29934628

    Open questions at the time
    • Cofactors at the MMP14 promoter not identified
  33. 2018 Medium

    Extended PROX1's NuRD-dependent Notch repression to colorectal cancer stem-like cells, showing reciprocal PROX1–Notch regulation.

    Evidence Co-IP, organoid knockout, and NOTCH1 promoter reporter assays

    PMID:30154153

    Open questions at the time
    • Direct binding to the NOTCH1 promoter within the NuRD context not fully resolved
  34. 2019 Medium

    Identified YAP/TAZ–TEAD with NuRD as a transcriptional repressor of Prox1, defining a Hippo-pathway input to lymphatic specification.

    Evidence LEC-specific Yap/Taz conditional knockout and hyperactivation with promoter occupancy assays

    PMID:30582452

    Open questions at the time
    • Reconciliation with the maintenance-promoting YAP/TAZ role at valves not resolved
  35. 2020 Medium

    Showed YAP/TAZ are required to maintain PROX1 in lymphatic and lymphovenous valves downstream of VEGF-C, revealing context-dependent Hippo control.

    Evidence Conditional Yap/Taz knockout with valve morphogenesis and PROX1 expression analysis

    PMID:33060128

    Open questions at the time
    • Mechanism reconciling positive valve role with negative specification role unresolved
  36. 2020 Medium

    Identified CELF1 as a 3' UTR-binding regulator that post-transcriptionally controls Prox1 protein in lens development.

    Evidence Lens-specific Celf1 conditional knockout, RNA-IP, and 3' UTR reporter assays

    PMID:32594240

    Open questions at the time
    • Interplay between CELF1 and miR-181a on the same 3' UTR not addressed
  37. 2020 Medium

    Revealed that PROX1 is hijacked by KSHV, interacting with ORF50 to promote viral lytic reactivation in LECs.

    Evidence Co-IP, ChIP on the KSHV genome, and genetic depletion with viral production assays

    PMID:32518203

    Open questions at the time
    • Whether host gene programs are co-opted not defined
  38. 2021 Medium

    Linked mitochondrial complex III activity to epigenetic control of the Prox1–Vegfr3 loop via H3K4me3/H3K27ac at LEC fate loci.

    Evidence LEC-specific complex III subunit deletion with histone-mark ChIP and gene expression

    PMID:33931446

    Open questions at the time
    • Metabolite intermediary connecting respiration to histone marks not pinpointed
  39. 2022 High

    Defined AMPK phosphorylation of PROX1 at Ser79 as a degradation switch recruiting CUL4-DDB1, coupling energy status to PROX1 stability and BCAA/mTOR metabolism.

    Evidence AMPK modulation, Ser79 mutagenesis, CUL4-DDB1 Co-IP, ubiquitination, and metabolic assays

    PMID:36433955

    Open questions at the time
    • Tissue contexts where this degradation operates not fully mapped
  40. 2022 Medium

    Connected lipophagy-driven mitochondrial metabolism to PROX1 target gene expression, showing acetyl-CoA availability tunes VEGFR3 and lymphangiogenesis.

    Evidence LEC-specific Atg5 knockout with metabolic profiling and acetate rescue

    PMID:35589749

    Open questions at the time
    • Direct epigenetic step on PROX1 targets not pinpointed
  41. 2022 Medium

    Identified PROX1–hnRNPK interaction as an oncogenic mechanism stabilizing hnRNPK and activating Wnt/β-catenin in breast cancer metastasis.

    Evidence Co-IP, ubiquitination assays, Wnt reporter, and in vivo metastasis model

    PMID:35342346

    Open questions at the time
    • Direct effect of PROX1 on hnRNPK ubiquitination machinery not resolved
  42. 2023 High

    Defined a PROX1 autoregulatory enhancer bound by GATA2/FOXC2/NFATC1/PROX1 and showed that disrupting its GATA2 site causes lymphatic defects and de-represses hemogenic potential.

    Evidence Precise genome editing of the GATA2 site, ChIP occupancy, and conditional knockout phenotyping

    PMID:36697821

    Open questions at the time
    • Hierarchy among the four enhancer-binding factors not fully ordered
  43. 2023 High

    Established a PROX1→FOXC2→PDGF-B axis in cardiac valvular endothelium that prevents myxomatous valve degeneration.

    Evidence VEC-specific conditional knockouts, pathway manipulation, echocardiography, and pharmacological rescue with imatinib

    PMID:37555328

    Open questions at the time
    • FOXC2-independent contribution to PDGF-B repression not quantified

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse PROX1 cofactor repertoire and post-translational/post-transcriptional inputs are integrated to select activator versus repressor output at a given locus in a given tissue remains unresolved.
  • No unified structural model of PROX1 partner-dependent DNA-element selectivity
  • Cross-talk between SUMOylation, AMPK-driven degradation, miR-181a, and CELF1 in vivo not integrated
  • Tissue-specific cofactor hierarchies largely uncatalogued

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 10 GO:0003677 DNA binding 6 GO:0140097 catalytic activity, acting on DNA 4
Localization
GO:0005634 nucleus 4
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-1430728 Metabolism 6 R-HSA-1643685 Disease 5 R-HSA-4839726 Chromatin organization 5 R-HSA-74160 Gene expression (Transcription) 5 R-HSA-162582 Signal Transduction 4
Partners
CTNNB1ERRAFOXC2HDAC3KDM1ANR2F2PGC1ATCF7L1
Complex memberships
HDAC3-PROX1 corepressor moduleLSD1/NuRD corepressor complexPROX1/COUP-TFII(NR2F2) heterodimerPROX1/β-catenin/TCF7L1 complex

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Ectopic expression of Prox1 in primary human blood vascular endothelial cells is sufficient to up-regulate lymphatic markers (podoplanin, VEGFR-3) and down-regulate blood vascular markers (laminin, VEGF-C, neuropilin-1, ICAM-1), reprogramming blood vascular endothelium toward a lymphatic phenotype. Prox1-deficient mice lack lymphatic vasculature and fail to acquire lymphatic endothelial cell fate. Adenoviral gene transfer, transient plasmid transfection, transcriptional profiling, RT-PCR, Western blotting, Prox1 knockout mice Developmental dynamics High 12412020
1999 Prox1 inactivation in mice causes abnormal cellular proliferation, downregulated expression of cell-cycle inhibitors Cdkn1b (p27KIP1) and Cdkn1c (p57KIP2), misexpression of E-cadherin, and inappropriate apoptosis, resulting in failure of lens cells to polarize and elongate and producing a hollow lens. Prox1 activity is required for progression of terminal fibre differentiation and elongation. Prox1 knockout mouse, immunostaining, gene expression analysis Nature genetics High 10080188
2003 Prox1 regulates cell cycle exit of retinal progenitor cells; cells lacking Prox1 are less likely to stop dividing, while ectopic Prox1 forces progenitor cells to exit the cell cycle. Prox1 is also necessary and sufficient for horizontal cell fate determination in the vertebrate retina. Prox1 knockout mice, ectopic Prox1 misexpression in postnatal progenitors, retinal cell fate analysis Nature genetics High 12692551
2008 Lymphatic endothelial cell identity depends on continuous Prox1 activity for its maintenance. Conditional down-regulation of Prox1 during embryonic, postnatal, or adult stages reprograms LECs into blood vascular endothelial cells, a Prox1-dependent, cell-autonomous process demonstrated by siRNA knockdown. Conditional Prox1 knockout mice (embryonic/postnatal/adult), siRNA knockdown in cultured LECs, phenotypic analysis Genes & development High 19056883
2008 PROX1 physically interacts with COUP-TFII to form a stable complex in LECs and other cell types. COUP-TFII acts as a coregulator of Prox1 to control lineage-specific genes including VEGFR-3, FGFR-3, and neuropilin-1, and is required with Prox1 to maintain LEC phenotype. Co-immunoprecipitation, gene expression analysis in LECs Blood Medium 18815287
2011 Development of the lymphovenous valve population and maintenance of Prox1 expression in venous ECs requires two functional copies of Prox1, mediated by COUP-TFII/Prox1 complex formation. Reduction in COUP-TFII/Prox1 complex formation in heterozygotes leads to loss of Prox1 expression and absent lymphovenous valves. Prox1 heterozygous mouse analysis, complex formation assay Genes & development Medium 22012621
2005 Prox1 directly binds to Prox1-response elements in the FGFR-3 promoter to activate FGFR-3 transcription as a direct target gene, establishing FGFR-3 as an initial transcriptional target of Prox1 during lymphatic cell fate specification. Ectopic Prox1 overexpression in blood vascular ECs, FGFR-3 promoter binding analysis, reporter assays Molecular biology of the cell Medium 16291864
2010 Prox1 is required for maturation of granule cells in the dentate gyrus during development and for maintenance of intermediate progenitors during adult neurogenesis. Prox1-expressing intermediate progenitors provide a non-cell autonomous feedback mechanism that controls adult neural stem cell self-maintenance; ectopic Prox1 expression induces premature differentiation of neural stem cells. Prox1 conditional knockout mice, BrdU labeling, immunostaining, ectopic expression PLoS biology High 20808958
2010 miR-181a binds the 3' UTR of Prox1 mRNA, causing translational inhibition and transcript degradation. Increased miR-181a in primary embryonic LECs reduces Prox1 mRNA and protein and reprograms LECs toward blood vascular phenotype; miR-181a antagomir in blood vascular ECs increases Prox1 levels. miR-181a is more highly expressed in blood vascular ECs than LECs. 3' UTR luciferase reporter assay, miR-181a overexpression/antagomir in primary embryonic LECs and BVECs, qRT-PCR, Western blot Blood High 20558617
2010 Prox1 interacts with ERRα and PGC-1α, occupies promoters of metabolic genes genome-wide, and inhibits the activity of the ERRα/PGC-1α transcriptional complex. Ablation of Prox1 and ERRα have opposite effects on respiratory capacity of liver cells, revealing a role for Prox1 in control of energy homeostasis. Co-immunoprecipitation, genome-wide ChIP, reporter assays, Prox1 knockdown in liver cells, respiratory capacity measurements Genes & development High 20194433
2009 Prox1 is SUMOylated at lysine 556 (K556) by SUMO-1. Mutation K556R reduces DNA binding and transcriptional activity of Prox1. SUMOylation controls Prox1's ability to induce VEGFR3 expression and lymphatic phenotypes in endothelial cells; SUMO-specific protease SENP2 reduces Prox1 sumoylation and Prox1-induced VEGFR3 expression. In vitro and in vivo sumoylation assays, mutagenesis (K556R), reporter assays, ectopic expression in EA.hy926 cells, SENP2 overexpression Journal of cell science High 19706680
2012 PROX1 and FOXC2 cooperate to mediate segregation of lymphatic-valve-forming cells and cell mechanosensory responses to shear stress. Mechanistically, PROX1, FOXC2, and flow coordinately control expression of connexin37 and activation of calcineurin/NFAT signaling, both required for assembly and delimitation of lymphatic valve territory. Conditional knockout mice (PROX1, FOXC2), shear stress in vitro assays, connexin37 and calcineurin loss-of-function, valve morphogenesis analysis Developmental cell High 22306086
2008 Cardiac-specific inactivation of Prox1 disrupts expression and localisation of sarcomeric proteins, causes myofibril disarray and growth-retarded hearts. Prox1 directly transcriptionally regulates the genes encoding structural proteins α-actinin, N-RAP, and zyxin, which maintain actin-α-actinin interaction as the fundamental sarcomere association. Cardiac-specific Prox1 conditional knockout, transcriptomic analysis, direct transcriptional regulation assays Development High 19091769
2014 Prox1 directly regulates Vegfr3 as a dosage-dependent in vivo target, and Vegfr3 in turn maintains Prox1 expression through a feedback loop that is the main sensing mechanism controlling the number of LEC progenitors. Vegfc-mediated activation of Vegfr3 signaling is necessary to maintain Prox1 expression in LEC progenitors. Multiple mouse genetic models, ChIP, gene expression analysis, Vegfc/Vegfr3 pathway manipulation Genes & development High 25274728
2010 Prox1 suppresses Notch1 gene expression by direct binding at the Notch1 promoter, counteracting Notch1 signaling in neural progenitor cells. Prox1-mediated suppression of Notch1 relieves its inhibition on neurogenesis, allowing NPCs to exit the cell cycle and differentiate. Loss of Prox1 in the chick neural tube prevents suppression of Notch1 outside the ventricular zone. ChIP assay, gain-of-function in chick neural tube, loss-of-function in chick neural tube, mouse NPC overexpression, promoter binding assays PLoS biology High 21203589
2013 COUP-TFII homodimers induce a venous EC fate by directly binding to promoters of Notch target genes HEY1 and HEY2, while COUP-TFII/PROX1 heterodimers lack this inhibitory effect. NR2F2/PROX1 heterodimers actively induce LEC-specific gene expression. PROX1 DNA binding also contributes to HEY1 and LEC-specific gene expression. Heterodimerization assays, promoter binding studies, knockdown experiments in endothelial cells, gene expression analysis Journal of cell science Medium 23345397
2013 PROX1 up-regulates HIF-1α transcription and stabilizes HIF-1α protein by recruiting histone deacetylase 1 (HDAC1) to prevent acetylation of HIF-1α, subsequently inducing an epithelial-mesenchymal transition response in HCC cells to promote metastasis. PROX1 knockdown and overexpression in HCC cells, in vitro migration/invasion assays, in vivo nude mouse metastasis model, co-IP for HDAC1 interaction Hepatology Medium 23505027
2013 Prox1 directly interacts with LSD1 (KDM1A) and recruits the LSD1/NuRD complex to the CYP7A1 promoter, co-repressing CYP7A1 transcription via H3K4 demethylation and histone deacetylation. This mechanism is involved in the physiological negative feedback inhibition of CYP7A1 by bile acids. Immunoprecipitation followed by mass spectrometry, GST pulldown (direct interaction), sequential ChIP, ChIP in siRNA knockdown cells, reporter assays PLoS one High 23626788
2016 Crystal structure of the SOX18 HMG box bound to a DNA element regulating Prox1 transcription was resolved at 1.75Å. SOX18 directly binds Prox1 promoter DNA; decoy oligonucleotides based on the Prox1-DNA element inhibit SOX18 DNA binding in vitro and suppress SOX18-dependent reporter activity in cells. X-ray crystallography (1.75Å), in vitro DNA binding assays, decoy oligonucleotide design and testing, luciferase reporter assay Nucleic acids research High 26939885
2011 ERRα, PROX1, and BMAL1 show extensive genomic co-occupancy in the liver. PROX1 is implicated in rhythmic control of metabolic outputs and acts as a corepressor in the ERRα transcriptional network, with genome-wide location analyses revealing transcriptional regulatory loops among these three factors controlling clock and metabolic gene networks. Genome-wide ChIP-seq (ERRα, PROX1, BMAL1), ERRα-null mouse phenotyping, locomotor activity assays PLoS genetics Medium 21731503
2017 HDAC3 and PROX1 form a corepressor module in vivo (identified by cross-linking mass spectrometry). HDAC3 and PROX1 co-localize extensively on the mouse liver genome and are co-recruited by HNF4α. The HDAC3-PROX1 module controls expression of a gene program regulating lipid homeostasis; hepatic-specific ablation of either component increases triglyceride content in liver. Cross-linking mass spectrometry (HDAC3 interactome), ChIP-seq, liver-specific conditional knockout of Prox1 and Hdac3 Nature communications High 28916805
2014 Prox1 directly binds to the 5' regulatory sequence of the Pdpn (podoplanin) gene in LECs (confirmed by ChIP and DNA pulldown assay) and regulates Pdpn gene expression at the transcriptional level as shown by luciferase reporter assay. ChIP assay, DNA pulldown assay, luciferase reporter assay Microvascular research Medium 24944097
2018 PROX1 suppresses transcription of MMP14 by binding and suppressing the MMP14 promoter. Prox1 deletion in murine dermal lymphatic vessels and siRNA knockdown in human LECs increased MMP14 expression. PROX1 ectopic expression reduced MMP14-dependent 3D invasiveness of breast cancer cells and angiogenic sprouting of blood endothelial cells. Prox1 conditional knockout in vivo, siRNA knockdown in LECs, promoter binding assay, 3D invasion assay Scientific reports Medium 29934628
2018 PROX1 forms a complex with β-catenin and the TCF/LEF transcription factor TCF7L1 to enhance Wnt/β-catenin signaling and promote FOXC2 and GATA2 expression in LECs. PROX1 thus directs lymphatic cell fate by acting as a Wnt signaling component. Co-immunoprecipitation, reporter assays, LEC-specific Wntless knockout mice, in vitro oscillatory shear stress assays Cell reports Medium 30332639
2014 Prox1 ablation in bipotent hepatoblasts dramatically reduces hepatocyte gene expression, leads to defective hepatocyte morphogenesis, and causes excessive cholangiocyte commitment and biliary hyperplasia, identifying Prox1 as a regulator of cell fate allocation in liver precursors. Conditional Prox1 knockout in hepatic progenitors, immunostaining, gene expression analysis Development High 24449835
2015 Prox1 activates the NFAT signalling pathway and is necessary and sufficient for the maintenance of slow muscle fibre type gene program. Prox1 is required for myoblast differentiation via bi-directional crosstalk with Notch1. Prox1-positive satellite cells differentiate into muscle fibres (shown by lineage tracing). Prox1 conditional knockout in satellite cells, Prox1 overexpression, lineage tracing, NFAT reporter assays Nature communications High 27731315
2008 Prox1 represses transcriptional activity of Gfi1 independently of Atoh1 in inner ear hair cells (luciferase assay). Prox1 transduction into cochlear outer hair cells caused their degeneration, consistent with Gfi1-deficient phenotype. Prox1 interacts with Atoh1 and Gfi1 and antagonizes the hair cell phenotype. Adenoviral Prox1 transduction in cochlear explants, luciferase transcriptional activity assay, comparison with Gfi1-deficient mice Developmental biology Medium 18652815
2014 Prox1 suppresses Olig2 expression by directly binding to the proximal promoter and K23 enhancer of the Olig2 gene locus in vivo (shown by ChIP). Prox1 is sufficient and necessary for suppression of Olig2 expression and control of MN versus V2 interneuron identity in ventral spinal cord. ChIP in mouse neural tube, gain- and loss-of-function in mouse NPCs and chick neural tube, promoter/enhancer reporter assays Journal of neuroscience High 25411508
2019 YAP and TAZ negatively regulate Prox1 transcription in LECs through recruitment of the NuRD (nucleosome remodeling and histone deacetylase) complex and endogenous binding of TEAD factors to the PROX1 promoter. LEC-specific YAP/TAZ hyperactivation profoundly downregulates Prox1 and impairs lymphatic specification. LEC-specific Yap/Taz conditional knockout and hyperactivation mouse models, promoter occupancy assays, NuRD complex recruitment assay Circulation research Medium 30582452
2022 AMPK phosphorylates PROX1 at Ser79, which enhances recruitment of the CUL4-DDB1 ubiquitin ligase to promote PROX1 ubiquitination and proteasomal degradation. PROX1 downregulation by AMPK activates branched-chain amino acid (BCAA) degradation through epigenetic modifications and inhibits mTOR signalling. AMPK activation/inhibition assays, site-directed mutagenesis (Ser79), co-IP for CUL4-DDB1 interaction, ubiquitination assays, epigenetic modification assays Nature communications High 36433955
2013 Transcriptional activation of Prox1 is directly controlled by HIF-1α and HIF-2α binding to a hypoxia-response element (HRE) in the Prox1 promoter/regulatory region, as demonstrated by EMSA and ChIP. HIF-1α/HIF-2α overexpression increases and knockdown decreases Prox1 promoter activity. EMSA, ChIP, HIF-1α/HIF-2α overexpression and knockdown, Prox1 promoter reporter assays FEBS letters Medium 23395615
2015 PROX1 promotes HCC cell proliferation and activates the Wnt/β-catenin pathway by upregulating β-catenin transcription via stimulation of the β-catenin promoter and enhancing nuclear translocation of β-catenin in HCC cells. PROX1 knockdown and overexpression in HCC cells, β-catenin promoter reporter assay, nuclear fractionation, in vivo xenograft Oncogene Medium 25684142
2018 PROX1 interacts with the NuRD complex to suppress the Notch pathway in colorectal cancer stem-like cells. PROX1 deletion increases Notch target gene expression and NOTCH1 promoter activity, demonstrating reciprocal regulation. Co-immunoprecipitation for NuRD complex interaction, PROX1 knockout in organoid cultures, reporter assays, gene expression analysis Cancer research Medium 30154153
2023 A PROX1 enhancer element bound by GATA2, FOXC2, NFATC1, and PROX1 itself is required for Prox1 expression in lymphatic endothelial cells. Disruption of the GATA2-binding site within this enhancer by genome editing caused profound lymphatic defects and revealed that lymphatic endothelium has haemogenic capacity ordinarily repressed by Prox1. Genome editing (5-nt deletion of GATA2-binding site), ChIP (occupancy by GATA2/FOXC2/NFATC1/PROX1), conditional mouse knockout, gene expression analysis Nature High 36697821
2021 Mitochondrial complex III activity regulates the critical Prox1-Vegfr3 feedback loop by controlling H3K4me3 and H3K27ac levels at the genomic loci of key LEC fate controllers (Vegfr3, Prox1), linking mitochondrial respiration to epigenetic control of LEC fate specification and maintenance. Conditional deletion of QPC (mitochondrial complex III subunit) in LECs, H3K4me3/H3K27ac ChIP, gene expression analysis Science advances Medium 33931446
2020 YAP and TAZ are required to maintain PROX1 expression in lymphatic valves and lymphovenous valves in response to VEGF-C signaling. Deletion of Yap and Taz in lymphatic vasculature of mouse embryos did not prevent valve formation but caused their degeneration with loss of PROX1 expression. Conditional Yap/Taz knockout in lymphatic vasculature, valve morphogenesis analysis, PROX1 expression analysis Development Medium 33060128
2022 Autophagy loss in LECs impairs lipid droplet degradation (lipophagy), reducing fatty acid oxidation, mitochondrial ATP production, acetyl-CoA/CoA ratio, and expression of lymphangiogenic PROX1 target genes including VEGFR3. Supplementing acetate (fatty acid precursor) rescues VEGFR3 levels and lymphangiogenesis in LEC-Atg5-/- mice, linking lipophagy to a mitochondrial-PROX1 gene expression circuit. LEC-specific Atg5 knockout mice, lipid droplet quantification, fatty acid oxidation assays, acetyl-CoA measurement, acetate supplementation rescue Nature communications Medium 35589749
2001 Prox1 and Six3 act antagonistically at the gamma-crystallin (CRYGD/e/f) promoter. A Prox1-responsive element was mapped between -151 and -174 and a Six3-responsive element between -101 and -123. Prox1 stimulates CRYGF promoter activity in cells lacking endogenous Prox1, acting as a transcriptional activator of gamma-crystallin genes. Cell transfection reporter assays, randomly mutated promoter fragment analysis, cell lines with and without endogenous Prox1 Nucleic acids research Medium 11139622
2008 Prox1 directly binds to the OL2 element and two additional upstream elements of the chicken betaB1-crystallin basal promoter. At the upstream sites, Prox1 mediates repression rather than activation, demonstrating that Prox1 function as transcriptional activator or repressor at this locus depends on the characteristics of the responsive DNA element and cellular context. DNase I footprinting, ChIP, transfection reporter assays in multiple lens cell types, transgenic mice Investigative ophthalmology & visual science Medium 18385074
2020 RNA-binding protein Celf1 post-transcriptionally regulates Prox1 protein levels in lens development via its 3' UTR. Celf1 lens-specific conditional knockout causes abnormal Prox1 protein distribution without changing Prox1 transcript levels. Celf1 protein binds Prox1 transcripts (RNA-immunoprecipitation), and Celf1 negatively controls Prox1 translation via its 3' UTR (reporter assays in KD and OE cells). Celf1 lens-specific conditional KO, immunostaining, qRT-PCR, RNA-immunoprecipitation, 3' UTR reporter assays in Celf1 KD and OE cells Human genetics Medium 32594240
2023 PROX1 interacts with KSHV ORF50 (viral initiator of lytic replication) protein and binds to the KSHV genome at the ORF50 promoter region, increasing ORF50 transactivation activity and spontaneous lytic gene expression and infectious virus release from LECs. Co-immunoprecipitation (PROX1-ORF50 interaction), ChIP on KSHV genome, PROX1 genetic depletion, lytic gene expression and viral production assays Cancer research Medium 32518203
2023 PROX1 inhibits PDGF-B expression in valvular endothelial cells (VECs) partially via FOXC2, preventing myxomatous degeneration of cardiac valves. Conditional Prox1 deletion from VECs caused FOXC2 downregulation and PDGF-B upregulation; conditional FOXC2 knockdown and PDGF-B overexpression recapitulated the Prox1 KO valve phenotype; pharmacological PDGF-B inhibition (imatinib) partially rescued the defects. VEC-specific conditional Prox1 knockout, FOXC2 knockdown and PDGF-B overexpression mouse models, echocardiography, histology, pharmacological inhibition Circulation research High 37555328
2022 PROX1 interacts with hnRNPK in breast cancer cells; this interaction inhibits ubiquitination of hnRNPK, which subsequently activates the WNT/β-catenin pathway to promote invasion and metastasis of breast cancer. Co-immunoprecipitation, ubiquitination assays, WNT pathway reporter, in vitro invasion assays, in vivo lung metastasis model International journal of biological sciences Medium 35342346
2015 ASCL1 complexes with NKX2-1 and PROX1 to co-regulate genes functioning in NOTCH signaling, catecholamine biosynthesis, and cell-cycle processes in ASCL1-high small-cell lung cancer. Chromatin landscape analysis (super-enhancer mapping), transcriptome analysis, co-occupancy analysis of ASCL1, NKX2-1, PROX1 in SCLC preclinical models iScience Low 34466783
2009 Prox1 (Prospero-related homeobox protein) represses HBV promoters in hepatocytes: for the ENII/Cp promoter, Prox1 serves as a corepressor of LRH-1 and downregulates LRH-1-mediated activation; for the Sp1 promoter, Prox1 partially represses activity by directly interacting with hepatocyte nuclear factor 1 (HNF1). Reporter-gene analysis of HBV promoters, co-immunoprecipitation for HNF1 interaction, HBV replication assays in hepatocyte cultures Journal of general virology Medium 19264593

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Prox1 is a master control gene in the program specifying lymphatic endothelial cell fate. Developmental dynamics : an official publication of the American Association of Anatomists 438 12412020
1999 Prox1 function is crucial for mouse lens-fibre elongation. Nature genetics 359 10080188
2012 Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. Developmental cell 337 22306086
2003 Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina. Nature genetics 336 12692551
2008 Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity. Genes & development 276 19056883
2010 Prox1 is required for granule cell maturation and intermediate progenitor maintenance during brain neurogenesis. PLoS biology 194 20808958
2014 The Prox1-Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors. Genes & development 153 25274728
2005 Prox1 promotes lineage-specific expression of fibroblast growth factor (FGF) receptor-3 in lymphatic endothelium: a role for FGF signaling in lymphangiogenesis. Molecular biology of the cell 151 16291864
2011 Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valves. Genes & development 145 22012621
2014 Lymphatic regulator PROX1 determines Schlemm's canal integrity and identity. The Journal of clinical investigation 143 25061877
2010 Prox1 expression is negatively regulated by miR-181 in endothelial cells. Blood 139 20558617
2006 Expression of Prox1 during mouse cochlear development. The Journal of comparative neurology 139 16538679
2008 Prox1 physically and functionally interacts with COUP-TFII to specify lymphatic endothelial cell fate. Blood 136 18815287
2007 Prox1 expression patterns in the developing and adult murine brain. Developmental dynamics : an official publication of the American Association of Anatomists 134 17117441
2010 The homeobox protein Prox1 is a negative modulator of ERR{alpha}/PGC-1{alpha} bioenergetic functions. Genes & development 125 20194433
2012 Transcription factor PROX1: its role in development and cancer. Cancer metastasis reviews 124 22733308
2008 Prox1 maintains muscle structure and growth in the developing heart. Development (Cambridge, England) 111 19091769
2015 Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 110 26377473
2010 Prox1 regulates the notch1-mediated inhibition of neurogenesis. PLoS biology 106 21203589
2003 Prox1, master regulator of the lymphatic vasculature phenotype. Cell and tissue research 105 12883994
2015 Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish. Cell reports 104 26655899
2013 PROX1 promotes hepatocellular carcinoma metastasis by way of up-regulating hypoxia-inducible factor 1α expression and protein stability. Hepatology (Baltimore, Md.) 90 23505027
2011 Genomic convergence among ERRα, PROX1, and BMAL1 in the control of metabolic clock outputs. PLoS genetics 84 21731503
2015 PROX1 promotes hepatocellular carcinoma proliferation and sorafenib resistance by enhancing β-catenin expression and nuclear translocation. Oncogene 83 25684142
2019 YAP and TAZ Negatively Regulate Prox1 During Developmental and Pathologic Lymphangiogenesis. Circulation research 82 30582452
2012 ProxTom lymphatic vessel reporter mice reveal Prox1 expression in the adrenal medulla, megakaryocytes, and platelets. The American journal of pathology 81 22310467
2022 PROX1 promotes breast cancer invasion and metastasis through WNT/β-catenin pathway via interacting with hnRNPK. International journal of biological sciences 73 35342346
2010 Expression of prox1, lymphatic endothelial nuclear transcription factor, in Kaposiform hemangioendothelioma and tufted angioma. The American journal of surgical pathology 70 20975337
2013 COUP-TFII orchestrates venous and lymphatic endothelial identity by homo- or hetero-dimerisation with PROX1. Journal of cell science 68 23345397
2014 Prox1 promotes expansion of the colorectal cancer stem cell population to fuel tumor growth and ischemia resistance. Cell reports 67 25242330
2014 PROX1 promotes metabolic adaptation and fuels outgrowth of Wnt(high) metastatic colon cancer cells. Cell reports 66 25242332
2021 Beyond PROX1: transcriptional, epigenetic, and noncoding RNA regulation of lymphatic identity and function. Developmental cell 59 33621491
2016 The transcription factor Prox1 is essential for satellite cell differentiation and muscle fibre-type regulation. Nature communications 58 27731315
2014 Prox1 and FOXC2 act as regulators of lymphangiogenesis and angiogenesis in oral squamous cell carcinoma. PloS one 58 24647631
2003 Mutations and aberrant DNA methylation of the PROX1 gene in hematologic malignancies. Genes, chromosomes & cancer 58 12874782
2018 Complementary Wnt Sources Regulate Lymphatic Vascular Development via PROX1-Dependent Wnt/β-Catenin Signaling. Cell reports 57 30332639
2008 Prox1 interacts with Atoh1 and Gfi1, and regulates cellular differentiation in the inner ear sensory epithelia. Developmental biology 57 18652815
2020 Prox1-positive cells monitor and sustain the murine intestinal epithelial cholinergic niche. Nature communications 56 31913277
2017 Development and Characterization of A Novel Prox1-EGFP Lymphatic and Schlemm's Canal Reporter Rat. Scientific reports 54 28717161
2017 An HDAC3-PROX1 corepressor module acts on HNF4α to control hepatic triglycerides. Nature communications 54 28916805
2022 Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis. Nature communications 52 35589749
2008 Altered regulation of Prox1-gene-expression in liver tumors. BMC cancer 52 18400094
2016 Structure and decoy-mediated inhibition of the SOX18/Prox1-DNA interaction. Nucleic acids research 50 26939885
2021 ASCL1, NKX2-1, and PROX1 co-regulate subtype-specific genes in small-cell lung cancer. iScience 49 34466783
1998 Characterization of the mouse Prox1 gene. Biochemical and biophysical research communications 49 9703987
2009 Sumoylation of Prox1 controls its ability to induce VEGFR3 expression and lymphatic phenotypes in endothelial cells. Journal of cell science 48 19706680
2017 Dynamic Expression of Sox2, Gata3, and Prox1 during Primary Auditory Neuron Development in the Mammalian Cochlea. PloS one 46 28118374
2014 Prox1 ablation in hepatic progenitors causes defective hepatocyte specification and increases biliary cell commitment. Development (Cambridge, England) 45 24449835
2003 Co-expression pattern of Shh with Prox1 and that of Nkx2.2 with Mash1 in mouse taste bud. Gene expression patterns : GEP 45 12915306
2015 A transgenic Prox1-Cre-tdTomato reporter mouse for lymphatic vessel research. PloS one 44 25849579
2008 Prox-1 promotes invasion of kaposiform hemangioendotheliomas. The Journal of investigative dermatology 44 18580962
2001 Antagonistic action of Six3 and Prox1 at the gamma-crystallin promoter. Nucleic acids research 44 11139622
2010 Expression of PROX1 Is a common feature of high-grade malignant astrocytic gliomas. Journal of neuropathology and experimental neurology 43 20084020
2019 Long non-coding RNA LINC00968 reduces cell proliferation and migration and angiogenesis in breast cancer through up-regulation of PROX1 by reducing hsa-miR-423-5p. Cell cycle (Georgetown, Tex.) 42 31213129
2015 Prospero-related homeobox 1 (Prox1) at the crossroads of diverse pathways during adult neural fate specification. Frontiers in cellular neuroscience 41 25674048
2020 YAP and TAZ maintain PROX1 expression in the developing lymphatic and lymphovenous valves in response to VEGF-C signaling. Development (Cambridge, England) 40 33060128
2020 Ras Pathways on Prox1 and Lymphangiogenesis: Insights for Therapeutics. Frontiers in cardiovascular medicine 40 33263009
2003 Expression of Prox1 defines regions of the avian otocyst that give rise to sensory or neural cells. The Journal of comparative neurology 40 12717709
2015 Positive regulation of β-catenin-PROX1 signaling axis by DBC1 in colon cancer progression. Oncogene 39 26477307
2021 Mitochondrial respiration controls the Prox1-Vegfr3 feedback loop during lymphatic endothelial cell fate specification and maintenance. Science advances 38 33931446
2013 Transcriptional activation of the Prox1 gene by HIF-1α and HIF-2α in response to hypoxia. FEBS letters 37 23395615
2011 Pancreas-specific deletion of Prox1 affects development and disrupts homeostasis of the exocrine pancreas. Gastroenterology 37 22178591
2023 A Prox1 enhancer represses haematopoiesis in the lymphatic vasculature. Nature 36 36697821
2018 PROX1 is a transcriptional regulator of MMP14. Scientific reports 36 29934628
2013 Prox1 directly interacts with LSD1 and recruits the LSD1/NuRD complex to epigenetically co-repress CYP7A1 transcription. PloS one 36 23626788
2018 Long noncoding RNA-antisense noncoding RNA in the INK4 locus accelerates wound healing in diabetes by promoting lymphangiogenesis via regulating miR-181a/Prox1 axis. Journal of cellular physiology 35 30565672
2015 Hepatic maturation of human iPS cell-derived hepatocyte-like cells by ATF5, c/EBPα, and PROX1 transduction. Biochemical and biophysical research communications 35 26679606
2022 AMPK induces degradation of the transcriptional repressor PROX1 impairing branched amino acid metabolism and tumourigenesis. Nature communications 31 36433955
2018 Transcription Factor PROX1 Suppresses Notch Pathway Activation via the Nucleosome Remodeling and Deacetylase Complex in Colorectal Cancer Stem-like Cells. Cancer research 30 30154153
2017 Prox1 Is a Marker for AII Amacrine Cells in the Mouse Retina. Frontiers in neuroanatomy 30 28529477
2014 Transcriptional regulation of podoplanin expression by Prox1 in lymphatic endothelial cells. Microvascular research 29 24944097
2009 Prospero-related homeobox protein (Prox1) inhibits hepatitis B virus replication through repressing multiple cis regulatory elements. The Journal of general virology 29 19264593
2012 The tumor suppressor p53 regulates c-Maf and Prox-1 to control lens differentiation. Current molecular medicine 27 22827438
2015 Prox1 Inhibits Proliferation and Is Required for Differentiation of the Oligodendrocyte Cell Lineage in the Mouse. PloS one 26 26709696
2007 Temporal and spatial expression of transcription factors FoxN4, Ptf1a, Prox1, Isl1 and Lim1 mRNA in the developing chick retina. Gene expression patterns : GEP 26 18006384
2020 Prox1 induces new lymphatic vessel formation and promotes nerve reconstruction in a mouse model of sciatic nerve crush injury. Journal of anatomy 25 32515838
2014 Prox1 regulates Olig2 expression to modulate binary fate decisions in spinal cord neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 24 25411508
2014 PROX1 gene is differentially expressed in oral cancer and reduces cellular proliferation. Medicine 24 25526434
2023 Exosomal circ_0026611 contributes to lymphangiogenesis by reducing PROX1 acetylation and ubiquitination in human lymphatic endothelial cells (HLECs). Cellular & molecular biology letters 22 36803975
2020 Oncogenic Herpesvirus Engages Endothelial Transcription Factors SOX18 and PROX1 to Increase Viral Genome Copies and Virus Production. Cancer research 22 32518203
2018 LncRNA PROX1-AS1 promotes proliferation, invasion, and migration in papillary thyroid carcinoma. Bioscience reports 22 30061172
2012 PROX1 overexpression inhibits protein kinase C beta II transcription through promoter DNA methylation. Genes, chromosomes & cancer 22 22833470
2020 The cataract-linked RNA-binding protein Celf1 post-transcriptionally controls the spatiotemporal expression of the key homeodomain transcription factors Pax6 and Prox1 in lens development. Human genetics 21 32594240
2016 DAB2IP regulates EMT and metastasis of prostate cancer through targeting PROX1 transcription and destabilizing HIF1α protein. Cellular signalling 21 27476001
2011 Characterization of Prox1 and VEGFR-3 expression and lymphatic phenotype in normal organs of mice lacking p50 subunit of NF-κB. Microcirculation (New York, N.Y. : 1994) 21 21166921
2009 Prox1 expression in rod precursors and Müller cells. Experimental eye research 21 19895810
2021 Long noncoding RNA GAS5 accelerates diabetic wound healing and promotes lymphangiogenesis via miR-217/Prox1 axis. Molecular and cellular endocrinology 20 33865922
2021 MiR-140-5p targets Prox1 to regulate the proliferation and differentiation of neural stem cells through the ERK/MAPK signaling pathway. Annals of translational medicine 20 33987369
2015 Prox1 identifies proliferating neuroblasts and nascent neurons during neurogenesis in sympathetic ganglia. Developmental neurobiology 20 25788138
2021 LncRNA PROX1-AS1 Facilitates Gastric Cancer Progression via miR-877-5p/PD-L1 Axis. Cancer management and research 19 33776485
2015 Nuclear PROX1 is Associated with Hypoxia-Inducible Factor 1α Expression and Cancer Progression in Esophageal Squamous Cell Carcinoma. Annals of surgical oncology 19 26310281
2011 Roles for MSI2 and PROX1 in hematopoietic stem cell activity. Current opinion in hematology 19 21577104
2013 Cell-cell interactions influence vascular reprogramming by Prox1 during embryonic development. PloS one 18 23341894
2017 High PROX1 expression in gastric cancer predicts better survival. PloS one 17 28854215
2015 Lack of Prox1 Downregulation Disrupts the Expansion and Maturation of Postnatal Murine β-Cells. Diabetes 17 26631740
2023 PROX1 Inhibits PDGF-B Expression to Prevent Myxomatous Degeneration of Heart Valves. Circulation research 16 37555328
2021 lncRNA PROX1-AS1 mediates the migration and invasion of placental trophoblast cells via the miR-211-5p/caspase-9 axis. Bioengineered 16 34288800
2018 Morphine regulates adult neurogenesis and contextual memory extinction via the PKCε/Prox1 pathway. Neuropharmacology 16 30170081
2014 Expression of Prox1, D2-40, and WT1 in spindle cell hemangioma. Journal of cutaneous pathology 16 24673328
2008 Dual roles for Prox1 in the regulation of the chicken betaB1-crystallin promoter. Investigative ophthalmology & visual science 16 18385074

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