Affinage

PROX1

Prospero homeobox protein 1 · UniProt Q92786

Length
737 aa
Mass
83.2 kDa
Annotated
2026-04-28
100 papers in source corpus 48 papers cited in narrative 48 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PROX1 is a homeodomain transcription factor that functions as a master cell-fate determinant across multiple tissues, most prominently serving as the obligate binary switch for lymphatic endothelial cell (LEC) identity. In LECs, PROX1 is both necessary and continuously required to suppress blood vascular gene programs and maintain lymphatic identity by directly binding and regulating promoters of VEGFR3, FGFR3, podoplanin, and integrin α9, operating through cofactor complexes with COUP-TFII, Ets-2, and β-catenin/TCF7L1, and participating in a self-sustaining PROX1–VEGFR3 feedback loop (PMID:11927535, PMID:19056883, PMID:25274728, PMID:18815287, PMID:30332639). Beyond the lymphatic vasculature, PROX1 specifies dentate gyrus granule cell versus CA3 pyramidal neuron fate, regulates hepatoblast allocation between hepatocyte and cholangiocyte lineages, maintains cardiac sarcomere integrity, controls slow muscle fiber identity via NFAT signaling, and modulates hematopoietic stem cell self-renewal (PMID:22791897, PMID:24449835, PMID:19091769, PMID:27731315, PMID:20621054). In liver, PROX1 partners with HDAC3 (recruited by HNF4α) and the LSD1/NuRD complex to co-repress lipid and bile acid metabolism genes, intersects with ERRα/PGC-1α to negatively regulate bioenergetic programs, and integrates circadian transcriptional networks through co-occupancy with BMAL1 (PMID:28916805, PMID:23626788, PMID:20194433, PMID:21731503). PROX1 activity is post-translationally tuned by SUMO-1 conjugation at K556 (required for DNA binding), AMPK-mediated phosphorylation at Ser79 triggering CUL4-DDB1 ubiquitin-dependent degradation, and NAA10-mediated acetylation that primes ubiquitination (PMID:19706680, PMID:36433955, PMID:36803975).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2001 Medium

    Early work established that PROX1 functions as a sequence-specific transcriptional activator, demonstrating direct binding to the γ-crystallin promoter and antagonism with Six3, providing the first evidence of PROX1 as a DNA-binding transcription factor with defined cis-elements.

    Evidence Promoter-reporter assays with mutational mapping in lens epithelial cells

    PMID:11139622

    Open questions at the time
    • Single lab; no in vivo validation of crystallin regulation
    • Whether these binding elements are conserved in non-lens contexts was unknown
  2. 2002 High

    The central question of whether PROX1 has a specific developmental role was answered: PROX1 is essential for lymphatic endothelial cell fate specification, as knockout embryos fail to generate LECs from venous endothelium, and ectopic PROX1 expression suffices to reprogram blood vascular ECs toward lymphatic identity.

    Evidence Prox1-null mouse embryos with marker analysis; adenoviral Prox1 gain-of-function in human BECs with transcriptional profiling

    PMID:11927535 PMID:12412020

    Open questions at the time
    • Whether PROX1 acts alone or requires cofactors was unknown
    • Direct transcriptional targets had not been identified
  3. 2005 High

    The question of which genes PROX1 directly regulates in LECs was addressed: PROX1 binds response elements in the FGFR3 promoter to directly activate transcription, identifying the first direct target gene of PROX1 in lymphatic fate specification.

    Evidence Promoter binding assays and siRNA knockdown in LECs with FGFR3 expression readout

    PMID:16291864

    Open questions at the time
    • Full repertoire of direct targets remained unknown
    • Whether FGFR3 is functionally required for PROX1-driven lymphangiogenesis was not tested
  4. 2007 High

    PROX1's functional output in LEC biology was extended beyond gene expression to cell behavior: PROX1 induces integrin α9 and VEGFR3, which together drive chemotactic migration toward VEGF-C while inhibiting sheet formation, connecting transcriptional targets to lymphatic morphogenetic behavior.

    Evidence Gain- and loss-of-function in LECs with migration and sheet formation assays

    PMID:17287396

    Open questions at the time
    • Whether integrin α9 is a direct transcriptional target was not shown by ChIP
    • In vivo validation of migration phenotype was lacking
  5. 2008 High

    Multiple studies resolved the temporal and tissue-specific requirements of PROX1: conditional deletion showed PROX1 is continuously required to maintain LEC identity at all life stages, while cardiac-specific KO revealed a separate role in sarcomere gene regulation, and PROX1/COUP-TFII complex formation was identified as essential for co-regulation of LEC genes.

    Evidence Inducible conditional KO mice at embryonic/postnatal/adult stages; cardiac-specific KO with microarray; reciprocal Co-IP of PROX1/COUP-TFII with ChIP on VEGFR3/FGFR3 promoters

    PMID:18815287 PMID:19056883 PMID:19091769

    Open questions at the time
    • Structural basis of PROX1/COUP-TFII interaction was undefined
    • Whether PROX1 recruits distinct cofactors in cardiac vs. lymphatic contexts was unknown
  6. 2008 High

    PROX1 was shown to function as a transcriptional repressor in non-vascular contexts: in inner ear hair cells, PROX1 represses Atoh1 and Gfi1, transcription factors critical for hair cell differentiation, demonstrating context-dependent activating versus repressing functions.

    Evidence Adenoviral PROX1 transduction in cochlear explants with luciferase reporter assays

    PMID:18652815

    Open questions at the time
    • No ChIP data for direct binding at Atoh1/Gfi1 loci
    • In vivo hair cell phenotype of Prox1 loss not examined in this study
  7. 2009 High

    Post-translational regulation of PROX1 was first characterized: SUMO-1 modification at K556 is required for DNA binding and transcriptional activation of lymphatic target genes, providing a mechanistic basis for fine-tuning PROX1 activity.

    Evidence In vitro/in vivo SUMOylation assays with K556R mutagenesis and SENP2 overexpression

    PMID:19706680

    Open questions at the time
    • Whether SUMOylation of PROX1 is dynamically regulated during lymphangiogenesis in vivo was untested
    • Structural mechanism of SUMO-enhanced DNA binding was unknown
  8. 2010 High

    PROX1's roles expanded beyond vascular and sensory systems: it was identified as a negative modulator of ERRα/PGC-1α-driven bioenergetic programs in liver through direct interaction and promoter co-occupancy, and as a required factor for granule cell maturation and intermediate progenitor maintenance in the hippocampal dentate gyrus.

    Evidence Genome-wide ChIP, Co-IP, respirometry in PROX1-ablated liver; conditional Prox1 KO and gain-of-function in mouse dentate gyrus

    PMID:20194433 PMID:20808958

    Open questions at the time
    • Specific metabolic gene targets of the PROX1/ERRα complex were not fully enumerated
    • Mechanism by which PROX1 intermediate progenitors non-cell-autonomously maintain stem cells was undefined
  9. 2011 High

    Multiple cofactors and regulatory inputs for PROX1 were resolved: Ets-2 was identified as a direct physical cofactor on the VEGFR3 promoter; PROX1 dosage was shown to control LEC progenitor number through COUP-TFII complex stoichiometry; Wnt/β-catenin was established as a direct upstream activator of PROX1 transcription in neural stem cells; and PROX1/ERRα/BMAL1 co-occupancy linked PROX1 to circadian metabolic regulation.

    Evidence Endogenous Co-IP/ChIP in LECs; Prox1 heterozygous mice; ChIP for β-catenin at Prox1 locus in neural stem cells; genome-wide co-binding analysis in liver

    PMID:21436036 PMID:21731503 PMID:21807940 PMID:22012621

    Open questions at the time
    • Whether Ets-2 and COUP-TFII cooperate or compete on the same promoters was unknown
    • Circadian regulation of PROX1 protein stability was not addressed
  10. 2012 High

    PROX1's cell-fate specification role was generalized to the hippocampus—postmitotic PROX1 loss converts dentate granule neurons to CA3 pyramidal identity—and its role in lymphatic valve morphogenesis was mechanistically linked to connexin37/calcineurin/NFAT signaling cooperating with FOXC2.

    Evidence Conditional Prox1 KO in postmitotic hippocampal neurons with reciprocal gain-of-function; PROX1/FOXC2 conditional deletions with shear stress experiments

    PMID:22306086 PMID:22791897

    Open questions at the time
    • Which PROX1 target genes mediate the granule-to-pyramidal fate switch was not identified
    • Whether PROX1 directly binds the connexin37 promoter was not shown
  11. 2013 High

    The mechanism of PROX1-mediated transcriptional repression was elucidated: PROX1 recruits the LSD1/NuRD complex to induce H3K4 demethylation and histone deacetylation at the CYP7A1 promoter in hepatocytes, establishing an epigenetic corepressor mechanism; separately, COUP-TFII/PROX1 heterodimer formation was shown to redirect COUP-TFII from venous to lymphatic gene programs.

    Evidence IP-MS identification of LSD1, sequential ChIP showing H3K4me/H3-H4ac changes; COUP-TFII/PROX1 Co-IP with promoter-binding and expression profiling in ECs

    PMID:23345397 PMID:23626788

    Open questions at the time
    • Whether LSD1/NuRD recruitment is a general mechanism at all PROX1-repressed genes was unknown
    • Structural basis of COUP-TFII homodimer versus heterodimer gene target switching was unresolved
  12. 2014 High

    A self-sustaining PROX1-VEGFR3 feedback loop was defined: PROX1 directly binds the Vegfr3 locus in a dosage-dependent manner, and VEGFC/VEGFR3 signaling maintains PROX1 expression, controlling LEC progenitor number; simultaneously, PROX1's roles in hepatoblast fate allocation, spinal cord V2/motor neuron specification (via Olig2 repression), and Schlemm's canal identity were established.

    Evidence Multiple mouse genetic models with ChIP at Vegfr3; hepatoblast-specific KO; ChIP at Olig2 locus in neural tube; ocular reporter mice

    PMID:24449835 PMID:25061877 PMID:25274728 PMID:25411508

    Open questions at the time
    • Signaling intermediates between VEGFR3 and PROX1 transcription were not identified
    • Genome-wide direct target repertoire in hepatoblasts was not mapped
  13. 2014 High

    PROX1 was linked to colorectal cancer stem cell biology as a dosage-dependent Wnt/β-catenin target that promotes stemness via annexin A1 induction, and SUMOylation of LRH-1 was shown to promote its corepressor interaction with PROX1 to regulate reverse cholesterol transport.

    Evidence Mouse adenoma models and 3D organoids with PROX1 deletion; LRH-1 K289R knock-in mice with PROX1 Co-IP and atherosclerosis phenotyping

    PMID:25176150 PMID:25242330

    Open questions at the time
    • Whether PROX1 directly binds annexin A1 or filamin A promoters was not shown
    • How SUMOylation-dependent PROX1/LRH-1 interaction is structurally mediated was unresolved
  14. 2016 High

    SOX18 was structurally validated as a direct upstream activator of PROX1: the crystal structure of SOX18 HMG domain bound to the Prox1 regulatory element was solved, and PROX1 was shown to maintain slow muscle fiber identity via NFAT signaling and Notch crosstalk.

    Evidence X-ray crystallography at 1.75Å with decoy oligo competition assays; lineage tracing and conditional KO/OE in skeletal muscle with NFAT reporter

    PMID:26939885 PMID:27731315

    Open questions at the time
    • Whether SOX18 acts combinatorially with other factors at the Prox1 promoter in vivo was not tested
    • Direct PROX1 targets in slow fiber gene program were not identified by ChIP
  15. 2017 High

    The PROX1/HDAC3 co-repressor module was mapped genome-wide in liver: cross-linking mass spectrometry and ChIP-seq revealed extensive co-recruitment by HNF4α, and dual conditional knockouts showed both factors control hepatic lipid homeostasis.

    Evidence XL-MS for HDAC3 interactome, ChIP-seq co-localization, liver-specific KO of HDAC3 and PROX1 with triglyceride measurements

    PMID:28916805

    Open questions at the time
    • Whether PROX1/HDAC3 interaction is direct or bridged entirely by HNF4α was not resolved
    • Dynamic regulation of this module during fasting/feeding cycles was not examined
  16. 2018 High

    Mechanotransduction was integrated into PROX1 signaling: oscillatory shear stress activates Wnt signaling that is channeled through a PROX1/β-catenin/TCF7L1 complex to drive lymphatic valve genes FOXC2 and GATA2; separately, PROX1 was shown to suppress Notch in colorectal cancer stem cells via NuRD complex recruitment, and YAP/TAZ-TEAD was identified as a negative regulator of PROX1 transcription through NuRD recruitment to the PROX1 promoter.

    Evidence Co-IP of PROX1/β-catenin/TCF7L1 with Wntless KO mice; Co-IP of PROX1/NuRD with NOTCH1 reporter in organoids; ChIP for TEAD/NuRD at PROX1 promoter in LECs with reciprocal genetic models

    PMID:30154153 PMID:30332639 PMID:30582452

    Open questions at the time
    • How PROX1 distinguishes Wnt-amplifying versus Notch-suppressing roles in different cell types was mechanistically unclear
    • Whether YAP/TAZ regulation of PROX1 operates in non-LEC contexts was untested
  17. 2021 High

    Metabolic regulation of the PROX1–VEGFR3 axis was uncovered: mitochondrial complex III activity maintains active histone marks (H3K4me3, H3K27ac) at PROX1 and VEGFR3 genomic loci, linking mitochondrial function to epigenetic maintenance of LEC identity.

    Evidence Conditional QPC knockout in mouse LECs with ChIP for histone modifications at Vegfr3/Prox1 loci

    PMID:33931446

    Open questions at the time
    • The metabolite(s) connecting complex III to histone methyltransferase/acetyltransferase activity were not identified
    • Whether this mechanism operates in adult lymphatic maintenance was not shown
  18. 2022 High

    Two modes of PROX1 post-translational degradation were defined: AMPK phosphorylates PROX1 at Ser79, recruiting CUL4-DDB1 E3 ligase for ubiquitin-dependent degradation that links energy sensing to BCAA catabolism and mTOR signaling; and lipophagy-derived acetyl-CoA sustains PROX1-dependent VEGFR3 expression, establishing a metabolic-transcriptional circuit in LECs.

    Evidence AMPK kinase assay with S79 mutagenesis and CUL4-DDB1 Co-IP; LEC-specific Atg5 KO with FAO and acetate rescue experiments

    PMID:35589749 PMID:36433955

    Open questions at the time
    • Whether AMPK-driven PROX1 degradation occurs in LECs or is liver-specific was not clarified
    • How acetyl-CoA mechanistically sustains PROX1 transcriptional activity (histone acetylation vs. protein modification) was not fully resolved
  19. 2023 High

    A critical Prox1 enhancer element was dissected at nucleotide resolution: a GATA2-binding site within the enhancer is co-occupied by GATA2, FOXC2, NFATC1, and PROX1 itself, and its disruption causes lethal lymphatic defects and acquisition of haemogenic capacity by LECs, revealing that PROX1 autoregulation suppresses alternative blood-forming fates.

    Evidence 5-nt enhancer deletion by genome editing in mice, ChIP for TF occupancy, RNA-seq, haematopoietic colony assays from mutant LECs

    PMID:36697821

    Open questions at the time
    • Whether PROX1 binding to its own enhancer is direct or mediated via GATA2 was not resolved
    • The haemogenic potential of adult (rather than embryonic) enhancer-mutant LECs was not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of PROX1's context-dependent switch between transcriptional activation and repression, the full genome-wide direct target repertoire across different tissues, and how PROX1 integrates metabolic, mechanical, and signaling inputs to maintain cell identity throughout life.
  • No full-length PROX1 structure or structure of PROX1 bound to any cofactor
  • Genome-wide direct target identification by CUT&RUN or similar in primary LECs at multiple developmental stages is lacking
  • Mechanism by which PROX1 suppresses haemogenic fate in LECs is unknown beyond enhancer requirement

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 5
Pathway
R-HSA-1266738 Developmental Biology 11 R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1430728 Metabolism 5 R-HSA-162582 Signal Transduction 5 R-HSA-4839726 Chromatin organization 2
Partners
CTNNB1ESRRAETS2FOXC2HDAC3KDM1ANR2F2TCF7L1
Complex memberships
PROX1/COUP-TFIIPROX1/HDAC3/HNF4αPROX1/LSD1/NuRDPROX1/β-catenin/TCF7L1

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Prox1 is required for lymphatic endothelial cell (LEC) fate specification: in Prox1-null embryos, venous endothelial cells that bud from cardinal veins fail to acquire lymphatic markers (VEGFR-3, LYVE-1, SLC) and instead retain a blood vascular phenotype (laminin, CD34 expression), establishing Prox1 as essential for the budding and lymphatic differentiation of venous endothelial cells. Genetic knockout (Prox1-/- mice), immunostaining, marker analysis The EMBO journal High 11927535
2002 Ectopic expression of Prox1 in primary human blood vascular endothelial cells is sufficient to reprogram them toward a lymphatic endothelial phenotype, upregulating lymphatic markers (podoplanin, VEGFR-3) and downregulating blood vascular markers (laminin, neuropilin-1, ICAM-1), establishing Prox1 as a master switch for LEC fate. Adenoviral gene transfer of Prox1 cDNA into blood vascular endothelial cells, transcriptional profiling, RT-PCR, Western blotting, immunostaining Developmental dynamics High 12412020
2008 Prox1 activity is continuously required to maintain LEC identity; conditional down-regulation of Prox1 during embryonic, postnatal, or adult stages causes LECs to revert to a blood vascular endothelial phenotype, demonstrating that Prox1 acts as a binary switch suppressing BEC identity and maintaining LEC identity in a cell-autonomous manner. Conditional (inducible) Prox1 knockout in mice, siRNA knockdown in cultured LECs, marker analysis Genes & development High 19056883
2008 Prox1 physically interacts with COUP-TFII to form a stable complex in lymphatic endothelial cells; this complex co-regulates LEC-specific genes including VEGFR-3, FGFR-3, and neuropilin-1, and COUP-TFII is required along with Prox1 to maintain the LEC phenotype. Co-immunoprecipitation, ChIP, gene expression analysis, loss-of-function studies Blood High 18815287
2005 Prox1 directly binds to Prox1-response elements in the FGFR-3 promoter to transcriptionally activate FGFR-3 expression specifically in lymphatic endothelial cells, identifying FGFR-3 as a direct Prox1 target gene during LEC fate specification. Prox1 overexpression in blood vascular ECs, promoter binding assays, siRNA knockdown of Prox1 in LECs, embryonic mouse immunostaining Molecular biology of the cell High 16291864
2007 Prox1 induces expression of integrin alpha9 in endothelial cells, which in turn inhibits sheet formation and stimulates cell motility; knockdown of Prox1 in LECs decreases integrin alpha9 and VEGFR3 expression and reduces chemotaxis toward VEGF-C. Prox1 overexpression, siRNA knockdown in LECs, migration assays, immunostaining in mouse embryos Molecular biology of the cell High 17287396
2009 SUMO-1 modifies Prox1 at lysine 556 (K556); mutation K556R reduces DNA binding and transcriptional activity of Prox1, and abolishes its ability to induce VEGFR3, FGFR3, and p57 expression and lymphatic phenotypes in endothelial cells; SENP2 overexpression reduces Prox1 sumoylation and Prox1-induced VEGFR3 expression. In vitro and in vivo sumoylation assays, mutagenesis (K556R), luciferase reporter assays, SENP2 overexpression Journal of cell science High 19706680
2010 Prox1 interacts with ERRalpha and PGC-1alpha, occupies promoters of metabolic genes genome-wide, and inhibits the transcriptional activity of the ERRalpha/PGC-1alpha complex; ablation of Prox1 and ERRalpha have opposite effects on respiratory capacity of liver cells, revealing Prox1 as a negative modulator of ERRalpha/PGC-1alpha bioenergetic functions. Co-immunoprecipitation, genome-wide ChIP, luciferase reporter assays, Prox1 ablation with respirometry Genes & development High 20194433
2009 NF-kappaB activates Prox1 expression in response to inflammatory stimuli, and Prox1 synergizes with the p50 subunit of NF-kappaB to drive VEGFR-3 promoter activity, thereby enhancing LEC responsiveness and lymphangiogenesis. In vivo time-course of inflammation-induced lymphangiogenesis, promoter reporter assays, NF-kappaB inhibition, siRNA knockdown in LECs Blood Medium 19901262
2011 Prox1 dosage controls the number of LEC progenitors; heterozygous Prox1 mice lack lymphovenous valves due to reduced COUP-TFII/Prox1 complex formation, impairing maintenance of Prox1 expression in venous endothelial cells. Prox1 heterozygous and conditional mouse models, Co-IP for COUP-TFII/Prox1 complex, immunostaining Genes & development High 22012621
2012 PROX1 and FOXC2, cooperating with shear stress/mechanotransduction, coordinately control connexin37 expression and calcineurin/NFAT signaling to mediate lymphatic valve formation; connexin37 and calcineurin are required for assembly and maintenance of lymphatic valve territory. Genetic mouse models (PROX1, FOXC2 conditional deletion), in vitro shear stress experiments, signaling analysis Developmental cell High 22306086
2014 Prox1 directly regulates Vegfr3 expression in a dosage-dependent manner in vivo; a Prox1-Vegfr3 feedback loop operates such that Vegfc-mediated activation of Vegfr3 signaling maintains Prox1 expression in LEC progenitors, controlling progenitor number and lymphatic vasculature formation. Multiple mouse genetic models (heterozygous, conditional KO), ChIP for Prox1 binding to Vegfr3 locus, Vegfc neutralization Genes & development High 25274728
2013 COUP-TFII (NR2F2) homodimers maintain venous EC identity by binding HEY1/HEY2 promoters to inhibit arterial differentiation, whereas NR2F2/PROX1 heterodimers shift toward LEC fate by inducing LEC-specific genes and allowing non-canonical HEY1/2 expression; PROX1 DNA binding is additionally required for some LEC-specific gene expression. Co-IP, promoter-binding assays, overexpression/knockdown of COUP-TFII and PROX1 in ECs, gene expression profiling Journal of cell science High 23345397
2011 Ets-2 physically interacts with endogenous Prox1 in LECs and acts as a transcriptional cofactor; both Prox1 and Ets-2 bind the VEGFR3 promoter in intact chromatin, and Ets-2 enhances Prox1-induced VEGFR3 expression and VEGF-C-directed LEC migration. Co-immunoprecipitation of endogenous proteins, ChIP on VEGFR3 promoter, in vivo peritonitis model, dominant-negative Ets-1 Journal of cell science High 21807940
2013 Prox1 directly interacts with LSD1 (identified by IP-MS), recruits the LSD1/NuRD complex to the CYP7A1 promoter in HepG2 cells, causing H3K4 demethylation and H3/H4 deacetylation to co-repress CYP7A1 transcription (bile acid synthesis); this mechanism mediates bile acid-induced negative feedback on CYP7A1. Immunoprecipitation/mass spectrometry, GST pulldown, sequential ChIP, siRNA knockdown, reporter assays PloS one High 23626788
2014 SUMOylation of LRH-1 at K289 promotes its interaction with PROX1 as a corepressor; abolishing LRH-1 SUMOylation (K289R mutation) compromises LRH-1/PROX1 interaction, increases reverse cholesterol transport gene expression and protects against atherosclerosis. SUMOylation-deficient knock-in mice, Co-IP for LRH-1/PROX1 interaction, gene expression analysis, atherosclerosis model Cell metabolism High 25176150
2017 PROX1 forms a co-repressor module with HDAC3 on the liver genome; HDAC3 and PROX1 are co-recruited by HNF4α, co-localize extensively genome-wide in mouse liver, and together regulate a lipid homeostasis gene program; hepatic-specific ablation of either HDAC3 or PROX1 increases liver triglyceride content. Cross-linking mass spectrometry (HDAC3 interactome), ChIP-seq for HDAC3 and PROX1, liver-specific knockout mice, metabolic phenotyping Nature communications High 28916805
2011 ERRalpha directly regulates PROX1 target genes in circadian metabolic control; genome-wide location analysis shows extensive overlap of ERRalpha, PROX1, and BMAL1 binding sites in liver, establishing PROX1 as part of a transcriptional regulatory loop between circadian and metabolic networks. Genome-wide ChIP (ERRalpha, PROX1, BMAL1), ERRalpha-null mice, circadian/metabolic phenotyping PLoS genetics High 21731503
2008 Cardiac-specific inactivation of Prox1 disrupts expression and localization of sarcomeric proteins (alpha-actinin, N-RAP, zyxin), causing myofibril disarray and growth-retarded hearts; Prox1 directly transcriptionally regulates genes encoding these structural proteins. Cardiac-specific conditional Prox1 knockout mice, microarray, qRT-PCR, immunostaining, ChIP/promoter assays Development (Cambridge, England) High 19091769
2010 Prox1 is required for granule cell maturation and intermediate progenitor maintenance in the dentate gyrus; ectopic Prox1 expression induces premature differentiation of neural stem cells, and Prox1-expressing intermediate progenitors non-cell-autonomously regulate adult neural stem cell self-maintenance. Conditional Prox1 knockout mice, ectopic Prox1 overexpression, BrdU labeling, immunostaining PLoS biology High 20808958
2011 Prox1 is a direct transcriptional target of canonical Wnt/beta-catenin-TCF/LEF signaling in neural stem cells; Prox1 overexpression enhances neuronal differentiation while shRNA knockdown impairs neuron generation in vitro and in the hippocampal niche, with a stage-specific role in initial granule cell differentiation but not maintenance of mature granule cells. TCF/LEF reporter assays, ChIP for beta-catenin at Prox1 locus, shRNA knockdown, retroviral Prox1 overexpression in adult hippocampus Proceedings of the National Academy of Sciences of the United States of America High 21436036
2012 Prox1 postmitotically functions as a cell fate determinant in the hippocampus: conditional elimination of Prox1 in immature dentate gyrus neurons causes them to adopt CA3 pyramidal neuron identity, while Prox1 overexpression in presumptive pyramidal cells suppresses that fate, demonstrating Prox1 specifies DG granule cell identity over CA3 pyramidal cell fate. Conditional Prox1 knockout in postmitotic neurons, Prox1 overexpression, immunostaining for cell type markers Development (Cambridge, England) High 22791897
2008 Prox1 acts as a transcriptional repressor of Atoh1 and Gfi1 in inner ear hair cells; adenoviral Prox1 transduction represses these transcription factors critical for hair cell differentiation, and luciferase assays show Prox1 can repress Gfi1 transcriptional activity independently of Atoh1. Adenoviral Prox1 transduction in cochlear explants, luciferase reporter assays, immunostaining Developmental biology High 18652815
2014 Prox1 ablation in hepatoblasts reduces expression of multiple hepatocyte genes and leads to defective hepatocyte morphogenesis, excessive commitment to cholangiocytes, and premature bile duct morphogenesis; Prox1 is a regulator of bipotent hepatoblast fate allocation between hepatocytes and cholangiocytes. Conditional (hepatoblast-specific) Prox1 knockout mice, immunostaining, gene expression analysis, histology Development (Cambridge, England) High 24449835
2011 Pancreas-specific deletion of Prox1 causes premature acinar cell differentiation, increased ductal cell proliferation, imbalanced claudin protein expression, altered duct morphogenesis, and progressive exocrine degeneration, identifying Prox1 as a regulator of tip progenitor expansion and duct morphogenesis in the exocrine pancreas. Pancreas-specific Prox1 conditional knockout mice, immunohistochemistry, electron microscopy, qRT-PCR, Western blot Gastroenterology High 22178591
2016 Prox1 activates NFAT signaling and is necessary and sufficient for maintenance of the slow muscle fibre gene program; Prox1-positive satellite cells differentiate into muscle fibres, and Prox1 is required for myoblast differentiation via bi-directional crosstalk with Notch1. Lineage tracing, conditional KO and overexpression in rodent/human skeletal muscle, NFAT reporter assays, Notch pathway analysis Nature communications High 27731315
2014 PROX1 transcriptional repression of podoplanin (PDPN) is direct: Prox1 binds to the 5' regulatory region of the Pdpn gene in LECs as demonstrated by ChIP and DNA pulldown, and luciferase assays confirm Prox1 binding regulates Pdpn gene expression. ChIP in LECs, DNA pulldown assay, luciferase reporter assay Microvascular research High 24944097
2016 Crystal structure of SOX18 HMG box bound to a DNA element regulating Prox1 transcription was solved at 1.75Å resolution; SOX18 directly binds the Prox1 promoter, and decoy oligonucleotides based on the Prox1-DNA element potently inhibit SOX18 binding and repress SOX18-dependent reporter gene expression, establishing SOX18 as an upstream regulator of Prox1. X-ray crystallography, in vitro DNA binding assays, decoy oligonucleotide competition, luciferase reporter assay Nucleic acids research High 26939885
2018 PROX1 forms a complex with beta-catenin and TCF7L1 to enhance Wnt/beta-catenin signaling in LECs, thereby promoting FOXC2 and GATA2 expression; oscillatory shear stress activates autocrine Wnt signaling in LECs that is channeled through this PROX1-containing complex. Co-immunoprecipitation of PROX1/beta-catenin/TCF7L1 complex, Wntless tissue-specific KO mice, in vitro shear stress, reporter assays Cell reports High 30332639
2019 YAP/TAZ hyperactivation suppresses PROX1 transcription by recruiting the NuRD (nucleosome remodeling and deacetylase) complex via TEAD binding to the PROX1 promoter; conversely, YAP/TAZ depletion upregulates Prox1 and disturbs lymphatic plexus patterning. LEC-specific Yap/Taz conditional KO and hyperactivation mice, ChIP for TEAD/NuRD at PROX1 promoter, reporter assays, cornea lymphangiogenesis model Circulation research High 30582452
2018 HHEX is an upstream transcriptional regulator of VEGFC, FLT4, and PROX1 in vascular and lymphatic development; genetic deletion in mouse and knockdown in human endothelial cells impairs sprouting angiogenesis from the cardinal vein and lymphangiogenesis. Zebrafish hhex mutants, tissue-specific genetic deletions in mouse, human EC knockdown, molecular pathway analysis Nature communications High 30006544
2014 PROX1 is a dosage-dependent direct target of beta-catenin/TCF signaling in intestinal tumors; PROX1 promotes colorectal cancer stem cell expansion through induction of annexin A1, reduction of filamin A, and promotion of autophagy/cell survival under hypoxia. In vivo mouse adenoma models, 3D organoid cultures, Prox1 deletion, AnnexinA1/Filamin A expression analysis Cell reports Medium 25242330
2018 PROX1 interacts with the NuRD complex to suppress the Notch pathway in colorectal cancer stem cells; PROX1 deletion increases Notch target gene expression and NOTCH1 promoter activity, revealing reciprocal suppression between PROX1 and Notch. Co-immunoprecipitation of PROX1/NuRD complex, NOTCH1 promoter reporter assays, PROX1 deletion in organoids and transgenic mouse models Cancer research High 30154153
2022 AMPK phosphorylates PROX1 at Ser79, promoting recruitment of CUL4-DDB1 ubiquitin ligase and subsequent PROX1 degradation; loss of PROX1 activates branched-chain amino acid (BCAA) degradation via epigenetic modifications and inhibits mTOR signaling. AMPK kinase assay, phospho-site mutagenesis, Co-IP of PROX1/CUL4-DDB1, PROX1 KO with BCAA metabolomics and mTOR signaling analysis Nature communications High 36433955
2009 PROX1 represses hepatitis B virus replication by acting as a corepressor of LRH-1 at the HBV enhancer II/core promoter and by interacting with HNF-1 to partially repress the preS1 promoter, reducing HBV antigen expression and genome replication in hepatocytes. Reporter gene analysis of HBV promoters, Co-IP/interaction studies with LRH-1 and HNF-1, HBV antigen expression assays in hepatocytes The Journal of general virology Medium 19264593
2014 Prox1 directly regulates Olig2 gene regulatory elements: ChIP in the mouse neural tube shows Prox1 binds the proximal Olig2 promoter and the K23 enhancer, suppressing Olig2 expression and thus controlling V2 interneuron versus motor neuron fate in ventral spinal cord. Gain/loss-of-function in mouse NPCs and chick neural tube, ChIP for Prox1 at Olig2 locus, luciferase reporter assays The Journal of neuroscience High 25411508
2013 Prox1 expression is transcriptionally activated by hypoxia through direct binding of HIF-1alpha and HIF-2alpha to a hypoxia-response element (HRE) in the Prox1 promoter/regulatory region, as confirmed by EMSA, ChIP, and promoter reporter assays. EMSA, ChIP, luciferase reporter assay, HIF overexpression and knockdown FEBS letters Medium 23395615
2022 Autophagy (lipophagy) in LECs supports fatty acid oxidation (FAO) and mitochondrial ATP production; when lipophagy is impaired, acetyl-CoA levels and expression of PROX1 target genes (including VEGFR3) decrease; restoring FAO via acetate supplementation rescues VEGFR3 levels and lymphangiogenesis, establishing a mitochondrial-PROX1 gene expression circuit. LEC-specific Atg5 knockout mice, DRP1 silencing, fatty acid oxidation assays, acetate rescue, corneal lymphangiogenesis model Nature communications High 35589749
2021 Mitochondrial complex III activity regulates the Prox1-Vegfr3 feedback loop; conditional deletion of QPC subunit in LECs results in loss of lymphatic vasculature through down-regulation of LEC fate regulators (Vegfr3, Prox1) associated with reduced H3K4me3 and H3K27ac at their genomic loci. Conditional QPC knockout in mouse LECs, ChIP for H3K4me3 and H3K27ac at Vegfr3/Prox1 loci, immunostaining Science advances High 33931446
2023 A Prox1 transcriptional enhancer element containing a GATA2-binding site is bound by GATA2, FOXC2, NFATC1, and PROX1 in LECs; genome editing of the enhancer (5-nt deletion of GATA2 site) causes profound lymphatic defects and perinatal death, and enhancer-mutant LECs acquire haemogenic capacity normally suppressed by Prox1 activity. Genome editing of enhancer in mice, ChIP for transcription factors, RNA-seq of mutant LECs, haematopoietic colony assays Nature High 36697821
2022 PROX1 interacts with hnRNPK in breast cancer cells; this interaction inhibits ubiquitination of hnRNPK, stabilizing it and activating WNT/beta-catenin signaling to promote invasion and metastasis. Co-immunoprecipitation, immunofluorescence, ubiquitination assay, luciferase promoter assay, in vitro transwell invasion, in vivo lung metastasis model International journal of biological sciences Medium 35342346
2023 Exosomal circ_0026611 interacts with NAA10 (N-alpha-acetyltransferase 10) to inhibit NAA10-mediated PROX1 acetylation; reduced PROX1 acetylation blocks its subsequent ubiquitination and degradation, thereby stabilizing PROX1 and promoting lymphangiogenesis in esophageal cancer. RNA immunoprecipitation, Co-IP, acetylation/ubiquitination assays in LECs, tube formation assay Cellular & molecular biology letters Medium 36803975
2014 PROX1 acquires lymphatic identity and controls Schlemm's canal (SC) integrity; SC originates from blood vessels postnatally but upregulates PROX1 to acquire lymphatic identity; PROX1 expression levels linearly correlate with SC functionality, and reduced AHO alters SC fate and PROX1 expression. Lymphatic/blood vascular reporter mice, ocular puncture model, immunostaining, PROX1 quantification in functional vs. pathological SCs The Journal of clinical investigation High 25061877
2020 PROX1 interacts with ORF50 (the viral initiator of lytic replication of KSHV) and binds to the KSHV genome at the ORF50 promoter region, increasing its transactivation activity and KSHV spontaneous lytic gene expression and infectious virus release from LECs. Co-immunoprecipitation of PROX1/ORF50, ChIP on KSHV genome, PROX1 genetic depletion, KSHV genome copy quantification, viral protein assays Cancer research High 32518203
2001 Prox1 and Six3 act antagonistically on the gamma-crystallin promoter: Prox1 activates CRYG promoter activity while Six3 represses it to ~10% of basal activity; specific response elements for each factor were mapped (Prox1-responsive: -151 to -174; Six3-responsive: -101 to -123). Promoter-reporter (luciferase) assays in lens epithelial cell lines, mutational analysis of promoter fragments, transfection in cells with/without endogenous Prox1 Nucleic acids research Medium 11139622
2012 Sox1 maintains neural progenitor identity by suppressing Prox1-mediated neurogenic cell divisions; loss of Sox1 increases Prox1-dependent cell cycle exit and neuronal differentiation, placing Sox1 upstream of Prox1 in the regulation of cortical neural progenitor pool size. Sox1-null mouse embryo-derived NPCs, Prox1 overexpression/knockdown, cell cycle analysis, in vivo and in vitro differentiation assays Stem cells (Dayton, Ohio) Medium 21280160
2012 Prox1 suppresses neuroblastoma cell proliferation by inducing p27-Kip1 and decreasing Cdc25A expression; rescue of Prox1's effects on Cdc25A and p27-Kip1 restores cell cycle progression, establishing the mechanistic basis for Prox1 antiproliferative activity in neuroblastoma. Inducible Prox1-overexpressing Neuro2A cells, shRNA knockdown, cell cycle analysis, SCID mouse xenograft, Western blotting for cyclins/Cdc25A/p27 Oncogene Medium 22508481
2010 Prox1 knockdown in hematopoietic stem cells (HSCs) leads to in vivo accumulation of primitive and differentiated cells and enhanced in vitro HSC activity; overexpression has the reverse phenotype, identifying Prox1 as a negative regulator/antagonist of HSC self-renewal. In vivo RNAi screen in mouse HSCs, bone marrow transplantation, Prox1 overexpression vector, gene expression profiling Cell stem cell Medium 20621054

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 An essential role for Prox1 in the induction of the lymphatic endothelial cell phenotype. The EMBO journal 755 11927535
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 435 12412020
2012 Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. Developmental cell 333 22306086
2008 Lymphatic endothelial cell identity is reversible and its maintenance requires Prox1 activity. Genes & development 274 19056883
2010 Prox1 is required for granule cell maturation and intermediate progenitor maintenance during brain neurogenesis. PLoS biology 194 20808958
2009 Inflammation induces lymphangiogenesis through up-regulation of VEGFR-3 mediated by NF-kappaB and Prox1. Blood 177 19901262
2008 Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype. Cancer cell 171 18455124
2011 Prospero-related homeobox 1 gene (Prox1) is regulated by canonical Wnt signaling and has a stage-specific role in adult hippocampal neurogenesis. Proceedings of the National Academy of Sciences of the United States of America 163 21436036
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
2014 The Prox1-Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors. Genes & development 149 25274728
2011 Prox1 dosage controls the number of lymphatic endothelial cell progenitors and the formation of the lymphovenous valves. Genes & development 144 22012621
2014 Lymphatic regulator PROX1 determines Schlemm's canal integrity and identity. The Journal of clinical investigation 141 25061877
2008 Prox1 physically and functionally interacts with COUP-TFII to specify lymphatic endothelial cell fate. Blood 135 18815287
2002 Prox1 is an early specific marker for the developing liver and pancreas in the mammalian foregut endoderm. Mechanisms of development 135 12351178
2007 Prox1 expression patterns in the developing and adult murine brain. Developmental dynamics : an official publication of the American Association of Anatomists 134 17117441
2007 Prox1 induces lymphatic endothelial differentiation via integrin alpha9 and other signaling cascades. Molecular biology of the cell 126 17287396
2010 An RNAi screen identifies Msi2 and Prox1 as having opposite roles in the regulation of hematopoietic stem cell activity. Cell stem cell 125 20621054
2010 The homeobox protein Prox1 is a negative modulator of ERR{alpha}/PGC-1{alpha} bioenergetic functions. Genes & development 124 20194433
2012 Transcription factor PROX1: its role in development and cancer. Cancer metastasis reviews 123 22733308
2012 Prox1 postmitotically defines dentate gyrus cells by specifying granule cell identity over CA3 pyramidal cell fate in the hippocampus. Development (Cambridge, England) 119 22791897
2008 Prox1 maintains muscle structure and growth in the developing heart. Development (Cambridge, England) 111 19091769
2015 Vegfc Regulates Bipotential Precursor Division and Prox1 Expression to Promote Lymphatic Identity in Zebrafish. Cell reports 104 26655899
2011 Genomic convergence among ERRα, PROX1, and BMAL1 in the control of metabolic clock outputs. PLoS genetics 82 21731503
2019 YAP and TAZ Negatively Regulate Prox1 During Developmental and Pathologic Lymphangiogenesis. Circulation research 80 30582452
2012 ProxTom lymphatic vessel reporter mice reveal Prox1 expression in the adrenal medulla, megakaryocytes, and platelets. The American journal of pathology 80 22310467
2004 IL-3 induces expression of lymphatic markers Prox-1 and podoplanin in human endothelial cells. Journal of immunology (Baltimore, Md. : 1950) 79 15585837
2022 PROX1 promotes breast cancer invasion and metastasis through WNT/β-catenin pathway via interacting with hnRNPK. International journal of biological sciences 71 35342346
2010 Expression of prox1, lymphatic endothelial nuclear transcription factor, in Kaposiform hemangioendothelioma and tufted angioma. The American journal of surgical pathology 69 20975337
2013 COUP-TFII orchestrates venous and lymphatic endothelial identity by homo- or hetero-dimerisation with PROX1. Journal of cell science 68 23345397
2018 HHEX is a transcriptional regulator of the VEGFC/FLT4/PROX1 signaling axis during vascular development. Nature communications 66 30006544
2014 Prox1 promotes expansion of the colorectal cancer stem cell population to fuel tumor growth and ischemia resistance. Cell reports 66 25242330
2014 Novel characterization and live imaging of Schlemm's canal expressing Prox-1. PloS one 65 24827370
2014 SUMOylation-dependent LRH-1/PROX1 interaction promotes atherosclerosis by decreasing hepatic reverse cholesterol transport. Cell metabolism 65 25176150
2014 PROX1 promotes metabolic adaptation and fuels outgrowth of Wnt(high) metastatic colon cancer cells. Cell reports 65 25242332
2011 Intravital two-photon microscopy of lymphatic vessel development and function using a transgenic Prox1 promoter-directed mOrange2 reporter mouse. Biochemical Society transactions 62 22103506
2007 Epigenetic silencing of the candidate tumor suppressor gene PROX1 in sporadic breast cancer. International journal of cancer 61 17415710
2013 A pathway for unicellular tube extension depending on the lymphatic vessel determinant Prox1 and on osmoregulation. Nature cell biology 60 23334499
2016 The transcription factor Prox1 is essential for satellite cell differentiation and muscle fibre-type regulation. Nature communications 58 27731315
2021 Beyond PROX1: transcriptional, epigenetic, and noncoding RNA regulation of lymphatic identity and function. Developmental cell 57 33621491
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
2018 Complementary Wnt Sources Regulate Lymphatic Vascular Development via PROX1-Dependent Wnt/β-Catenin Signaling. Cell reports 56 30332639
2017 An HDAC3-PROX1 corepressor module acts on HNF4α to control hepatic triglycerides. Nature communications 54 28916805
2011 Sox1 maintains the undifferentiated state of cortical neural progenitor cells via the suppression of Prox1-mediated cell cycle exit and neurogenesis. Stem cells (Dayton, Ohio) 53 21280160
2017 Development and Characterization of A Novel Prox1-EGFP Lymphatic and Schlemm's Canal Reporter Rat. Scientific reports 52 28717161
2008 Altered regulation of Prox1-gene-expression in liver tumors. BMC cancer 52 18400094
2022 Lipid droplet degradation by autophagy connects mitochondria metabolism to Prox1-driven expression of lymphatic genes and lymphangiogenesis. Nature communications 50 35589749
2016 Structure and decoy-mediated inhibition of the SOX18/Prox1-DNA interaction. Nucleic acids research 50 26939885
1998 Characterization of the mouse Prox1 gene. Biochemical and biophysical research communications 49 9703987
2017 Direct conversion of human fibroblasts into hepatocyte-like cells by ATF5, PROX1, FOXA2, FOXA3, and HNF4A transduction. Scientific reports 48 29192290
2009 Sumoylation of Prox1 controls its ability to induce VEGFR3 expression and lymphatic phenotypes in endothelial cells. Journal of cell science 48 19706680
2021 ASCL1, NKX2-1, and PROX1 co-regulate subtype-specific genes in small-cell lung cancer. iScience 47 34466783
2017 Dynamic Expression of Sox2, Gata3, and Prox1 during Primary Auditory Neuron Development in the Mammalian Cochlea. PloS one 45 28118374
2014 Prox1 ablation in hepatic progenitors causes defective hepatocyte specification and increases biliary cell commitment. Development (Cambridge, England) 45 24449835
2011 Ets family members induce lymphangiogenesis through physical and functional interaction with Prox1. Journal of cell science 45 21807940
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
2020 Curcumol attenuates liver sinusoidal endothelial cell angiogenesis via regulating Glis-PROX1-HIF-1α in liver fibrosis. Cell proliferation 44 32119185
2006 Loss of function of the candidate tumor suppressor prox1 by RNA mutation in human cancer cells. Neoplasia (New York, N.Y.) 44 17217617
2001 Antagonistic action of Six3 and Prox1 at the gamma-crystallin promoter. Nucleic acids research 44 11139622
2015 A transgenic Prox1-Cre-tdTomato reporter mouse for lymphatic vessel research. PloS one 43 25849579
2004 The homeobox transcription factor Prox1 is highly conserved in embryonic hepatoblasts and in adult and transformed hepatocytes, but is absent from bile duct epithelium. Anatomy and embryology 42 15232737
2015 Prospero-related homeobox 1 (Prox1) at the crossroads of diverse pathways during adult neural fate specification. Frontiers in cellular neuroscience 40 25674048
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
2020 Ras Pathways on Prox1 and Lymphangiogenesis: Insights for Therapeutics. Frontiers in cardiovascular medicine 39 33263009
2015 Positive regulation of β-catenin-PROX1 signaling axis by DBC1 in colon cancer progression. Oncogene 39 26477307
2015 Aberrant Activation of Notch Signaling Inhibits PROX1 Activity to Enhance the Malignant Behavior of Thyroid Cancer Cells. Cancer research 39 26609053
2013 Transcriptional activation of the Prox1 gene by HIF-1α and HIF-2α in response to hypoxia. FEBS letters 37 23395615
2007 Lymphatic reprogramming of microvascular endothelial cells by CEA-related cell adhesion molecule-1 via interaction with VEGFR-3 and Prox1. Blood 37 17761831
2006 Prospero-related homeobox 1 (Prox1) is a stable hepatocyte marker during liver development, injury and regeneration, and is absent from "oval cells". Histochemistry and cell biology 37 16770575
2013 Prox1 directly interacts with LSD1 and recruits the LSD1/NuRD complex to epigenetically co-repress CYP7A1 transcription. PloS one 36 23626788
2012 Genetic and molecular insights into the role of PROX1 in glucose metabolism. Diabetes 36 23274905
2011 Pancreas-specific deletion of Prox1 affects development and disrupts homeostasis of the exocrine pancreas. Gastroenterology 36 22178591
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
2023 A Prox1 enhancer represses haematopoiesis in the lymphatic vasculature. Nature 34 36697821
2021 Mitochondrial respiration controls the Prox1-Vegfr3 feedback loop during lymphatic endothelial cell fate specification and maintenance. Science advances 34 33931446
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 34 30565672
2008 Crucial role of zebrafish prox1 in hypothalamic catecholaminergic neurons development. BMC developmental biology 33 18331627
2012 Prox1 suppresses the proliferation of neuroblastoma cells via a dual action in p27-Kip1 and Cdc25A. Oncogene 31 22508481
2022 AMPK induces degradation of the transcriptional repressor PROX1 impairing branched amino acid metabolism and tumourigenesis. Nature communications 30 36433955
2018 Transcription Factor PROX1 Suppresses Notch Pathway Activation via the Nucleosome Remodeling and Deacetylase Complex in Colorectal Cancer Stem-like Cells. Cancer research 29 30154153
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
2015 A pooled shRNA screen for regulators of primary mammary stem and progenitor cells identifies roles for Asap1 and Prox1. BMC cancer 28 25879659
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
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 gene is differentially expressed in oral cancer and reduces cellular proliferation. Medicine 24 25526434
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 23 25411508
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
2021 Long noncoding RNA GAS5 accelerates diabetic wound healing and promotes lymphangiogenesis via miR-217/Prox1 axis. Molecular and cellular endocrinology 21 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
2019 Transcription Factor Prospero Homeobox 1 (PROX1) as a Potential Angiogenic Regulator of Follicular Thyroid Cancer Dissemination. International journal of molecular sciences 20 31717665
2011 Transcriptional factor Prox1 plays an essential role in the antiproliferative action of interferon-γ in esophageal cancer cells. Annals of surgical oncology 20 21452064
2009 Prox1 expression in rod precursors and Müller cells. Experimental eye research 20 19895810
2009 VEGF-A/HGF induce Prox-1 expression in the chick embryo chorioallantoic membrane lymphatic vasculature. Clinical and experimental medicine 20 20033752
2016 Fucoidan inhibits lymphangiogenesis by downregulating the expression of VEGFR3 and PROX1 in human lymphatic endothelial cells. Oncotarget 19 27203545
2015 Prox1 identifies proliferating neuroblasts and nascent neurons during neurogenesis in sympathetic ganglia. Developmental neurobiology 19 25788138
2011 Roles for MSI2 and PROX1 in hematopoietic stem cell activity. Current opinion in hematology 19 21577104