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Gene Review

PROX1  -  prospero homeobox 1

Homo sapiens

Synonyms: Homeobox prospero-like protein PROX1, PROX-1, Prospero homeobox protein 1
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Disease relevance of PROX1


High impact information on PROX1

  • Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina [6].
  • Cells lacking Prox1 are less likely to stop dividing, and ectopic expression of Prox1 forces progenitor cells to exit the cell cycle [6].
  • During retinogenesis, Prox1 can be detected in differentiating horizontal, bipolar and AII amacrine cells [6].
  • The expression pattern of the Prox1 homeobox gene suggests it has a role in a variety of embryonic tissues, including lens [7].
  • Signals mediated by vascular endothelial growth factor-C, the homeodomain transcription factor PROX1 and the forkhead transcription factor FOXC2 have been implicated in the growth, morphogenesis and hierarchic organization of the lymphatic vascular network [8].

Chemical compound and disease context of PROX1

  • However neither bacterially expressed Sp1 516C or vaccinia virus expressed full-length Sp1 778C bound to the Prox or Pyr sequences in DNase I footprints or gel shift assays [9].

Biological context of PROX1


Anatomical context of PROX1


Associations of PROX1 with chemical compounds

  • In conclusion, although Prox-1 expression in vascular lesions/tumors was not entirely restricted to tumors with known lymphatic differentiation, CD 31/Prox-1 double-immunolabeling can be used as an adjunct marker to identify lymphatic vessels in routinely processed formalin-fixed, paraffin-embedded samples [12].
  • Despite lacking defined catalytic motifs, PROX induced an early Jak-independent signal, including tyrosine phosphorylation of IL-2Rbeta and the tyrosine phosphatase SHP-2 [14].
  • Prox-1 immunohistochemistry and pulse-chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat [15].
  • Supershift assays with a polyclonal anti-Sp1 antisera confirmed that Sp1 was part of the complex formed with the Prox/Pyr probe [9].
  • Consequently, Pt/TiO2 shows substantially lower selectivities toward CO oxidation under PROX conditions than Pt/gamma-Al2O3 [16].

Physical interactions of PROX1

  • Gel shift assays reveal that Prox1 impairs the binding of hLRH-1 to the promoter of human cyp7a1 gene [17].

Regulatory relationships of PROX1


Other interactions of PROX1

  • In hLRH-1 LBD, helices 2 and 10 are essential for Prox1 recruitment [17].
  • Recently this task has become feasible thanks to the identification of new lymphatic markers such as Podoplanin, Lyve-1, Prox-1 and D2-40 [20].
  • Using a yeast two-hybrid assay, we found that Prox1 strongly and specifically interacted with hepatocyte nuclear factor (HNF)4alpha, an important transactivator of the human CYP7A1 gene in bile acid synthesis and phosphoenolpyruvate carboxykinase (PEPCK) gene in gluconeogenesis [11].
  • Analysis of the expression of lymphendothelial markers VEGFR-3, Prox, and LYVE revealed concordant results, indicating that quantification of lymphendothelial cells is possible by qPCR [21].
  • METHODS: Seventeen paraffin-embedded specimens of carcinomas of the bilary system were subjected to loss-of-heterozygosity (LOH) and microsatellite instability analyses, methylation-specific polymerase-chain reaction (MSP) and immunohistochemical detection of PROX1 protein in tumor sections [3].

Analytical, diagnostic and therapeutic context of PROX1


  1. Mutations and aberrant DNA methylation of the PROX1 gene in hematologic malignancies. Nagai, H., Li, Y., Hatano, S., Toshihito, O., Yuge, M., Ito, E., Utsumi, M., Saito, H., Kinoshita, T. Genes Chromosomes Cancer (2003) [Pubmed]
  2. Lymphatic reprogramming of blood vascular endothelium by Kaposi sarcoma-associated herpesvirus. Hong, Y.K., Foreman, K., Shin, J.W., Hirakawa, S., Curry, C.L., Sage, D.R., Libermann, T., Dezube, B.J., Fingeroth, J.D., Detmar, M. Nat. Genet. (2004) [Pubmed]
  3. Prospero-related homeobox 1 (PROX1) is frequently inactivated by genomic deletions and epigenetic silencing in carcinomas of the bilary system. Laerm, A., Helmbold, P., Goldberg, M., Dammann, R., Holzhausen, H.J., Ballhausen, W.G. J. Hepatol. (2007) [Pubmed]
  4. LYVE-1 is not restricted to the lymph vessels: expression in normal liver blood sinusoids and down-regulation in human liver cancer and cirrhosis. Mouta Carreira, C., Nasser, S.M., di Tomaso, E., Padera, T.P., Boucher, Y., Tomarev, S.I., Jain, R.K. Cancer Res. (2001) [Pubmed]
  5. Infantile hemangiomas are arrested in an early developmental vascular differentiation state. Dadras, S.S., North, P.E., Bertoncini, J., Mihm, M.C., Detmar, M. Mod. Pathol. (2004) [Pubmed]
  6. Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina. Dyer, M.A., Livesey, F.J., Cepko, C.L., Oliver, G. Nat. Genet. (2003) [Pubmed]
  7. Prox1 function is crucial for mouse lens-fibre elongation. Wigle, J.T., Chowdhury, K., Gruss, P., Oliver, G. Nat. Genet. (1999) [Pubmed]
  8. Molecular lymphangiogenesis: new players. Tammela, T., Petrova, T.V., Alitalo, K. Trends Cell Biol. (2005) [Pubmed]
  9. Targeting of Sp1 to a non-Sp1 site in the human neurofilament (H) promoter via an intermediary DNA-binding protein. Elder, G.A., Liang, Z., Li, C., Lazzarini, R.A. Nucleic Acids Res. (1992) [Pubmed]
  10. Functional conservation of interactions between a homeodomain cofactor and a mammalian FTZ-F1 homologue. Steffensen, K.R., Holter, E., Båvner, A., Nilsson, M., Pelto-Huikko, M., Tomarev, S., Treuter, E. EMBO Rep. (2004) [Pubmed]
  11. A Prospero-related homeodomain protein is a novel co-regulator of hepatocyte nuclear factor 4alpha that regulates the cholesterol 7alpha-hydroxylase gene. Song, K.H., Li, T., Chiang, J.Y. J. Biol. Chem. (2006) [Pubmed]
  12. Differential Prox-1 and CD 31 expression in mucousae, cutaneous and soft tissue vascular lesions and tumors. Reis, R.M., Reis-Filho, J.S., Longatto Filho, A., Tomarev, S., Silva, P., Lopes, J.M. Pathol. Res. Pract. (2005) [Pubmed]
  13. Prox1 is a marker of ectodermal placodes, endodermal compartments, lymphatic endothelium and lymphangioblasts. Rodriguez-Niedenführ, M., Papoutsi, M., Christ, B., Nicolaides, K.H., von Kaisenberg, C.S., Tomarev, S.I., Wilting, J. Anat. Embryol. (2001) [Pubmed]
  14. Requirement for an initial signal from the membrane-proximal region of the interleukin 2 receptor gamma(c) chain for Janus kinase activation leading to T cell proliferation. Nelson, B.H., McIntosh, B.C., Rosencrans, L.L., Greenberg, P.D. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  15. Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy. Parent, J.M., Elliott, R.C., Pleasure, S.J., Barbaro, N.M., Lowenstein, D.H. Ann. Neurol. (2006) [Pubmed]
  16. Effects of reduction temperature and metal-support interactions on the catalytic activity of Pt/gamma-Al2O3 and Pt/TiO2 for the oxidation of CO in the presence and absence of H2. Alexeev, O.S., Chin, S.Y., Engelhard, M.H., Ortiz-Soto, L., Amiridis, M.D. The journal of physical chemistry. B, Condensed matter, materials, surfaces, interfaces & biophysical. (2005) [Pubmed]
  17. Prospero-related homeobox (Prox1) is a corepressor of human liver receptor homolog-1 and suppresses the transcription of the cholesterol 7-alpha-hydroxylase gene. Qin, J., Gao, D.M., Jiang, Q.F., Zhou, Q., Kong, Y.Y., Wang, Y., Xie, Y.H. Mol. Endocrinol. (2004) [Pubmed]
  18. IL-3 induces expression of lymphatic markers Prox-1 and podoplanin in human endothelial cells. Gröger, M., Loewe, R., Holnthoner, W., Embacher, R., Pillinger, M., Herron, G.S., Wolff, K., Petzelbauer, P. J. Immunol. (2004) [Pubmed]
  19. Prox1 expression patterns in the developing and adult murine brain. Lavado, A., Oliver, G. Dev. Dyn. (2007) [Pubmed]
  20. Isolation, purification, and heterogeneity of human lymphatic endothelial cells from different tissues. Garrafa, E., Trainini, L., Benetti, A., Saba, E., Fezzardi, L., Lorusso, B., Borghetti, P., Bottio, T., Ceri, E., Portolani, N., Bonardlli, S., Giulini, S.M., Annibale, G., Corradi, A., Imberti, L., Caruso, A. Lymphology. (2005) [Pubmed]
  21. Determination of Microvessel Density by Quantitative Real-time PCR in Esophageal Cancer: Correlation with Histologic Methods, Angiogenic Growth Factor Expression, and Lymph Node Metastasis. Loges, S., Clausen, H., Reichelt, U., Bubenheim, M., Erbersdobler, A., Schurr, P., Yekebas, E., Schuch, G., Izbicki, J., Pantel, K., Bokemeyer, C., Fiedler, W. Clin. Cancer Res. (2007) [Pubmed]
  22. First year changes of myocardial lymphatic endothelial markers in heart transplant recipients. Geissler, H.J., Dashkevich, A., Fischer, U.M., Fries, J.W., Kuhn-Régnier, F., Addicks, K., Mehlhorn, U., Bloch, W. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. (2006) [Pubmed]
  23. The transcription factor Prox1 is a marker for lymphatic endothelial cells in normal and diseased human tissues. Wilting, J., Papoutsi, M., Christ, B., Nicolaides, K.H., von Kaisenberg, C.S., Borges, J., Stark, G.B., Alitalo, K., Tomarev, S.I., Niemeyer, C., Rössler, J. FASEB J. (2002) [Pubmed]
  24. Prox1 is differentially localized during lens development. Duncan, M.K., Cui, W., Oh, D.J., Tomarev, S.I. Mech. Dev. (2002) [Pubmed]
  25. Regulation of Prox 1 during lens regeneration. Del Rio-Tsonis, K., Tomarev, S.I., Tsonis, P.A. Invest. Ophthalmol. Vis. Sci. (1999) [Pubmed]
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