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Gene Review

EPO  -  erythropoietin

Homo sapiens

Synonyms: EP, Erythropoietin, MVCD2
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Disease relevance of EPO


Psychiatry related information on EPO


High impact information on EPO


Chemical compound and disease context of EPO


Biological context of EPO

  • This unliganded EPOR dimer is formed from self-association of the same key binding site residues that interact with EPO-mimetic peptide and EPO ligands [22].
  • Furthermore, high concentrations of anti-EPO-neutralizing antibody abrogated erythropoiesis in cultures without exogenous EPO [23].
  • Because rHu-EPO is currently used widely with an excellent safety profile, clinical trials evaluating its potential to prevent motor neuron apoptosis and the neurological deficits that occur as a consequence of ischemic injury are warranted [2].
  • High concentrations of EPO occurred in patients experiencing significant hypotension despite routine transfusions for hematocrit < 42% [24].
  • Inhibitors of phosphatidylinositide 3-kinase and Src kinases suppressed EPO-dependent phosphorylation of Gab2 [25].

Anatomical context of EPO


Associations of EPO with chemical compounds


Physical interactions of EPO


Enzymatic interactions of EPO


Regulatory relationships of EPO


Other interactions of EPO

  • However, structures of agonist and antagonist peptide complexes of EPOR, as well as an EPO-EPOR complex, have shown that the actual dimer configuration is critical for the biological response and signal efficiency [22].
  • Thus, EPOR and JAK2 association seems to be important for EPO responsiveness in CTLL-2 cells [41].
  • These IL-2- and EPO-induced STATs have an identical DNA binding specificity and immunoreactivity [41].
  • Hypoxia-induced VEGF and Epo mRNA synthesis were similarly inhibited by E1A [42].
  • Individual day 14 to 18 CFU-GEMM or BFU-E colonies were removed from primary cultures and reseeded into secondary methylcellulose cultures containing a combination of Epo, MGF, and rhu granulocyte-macrophage colony-stimulating factor (GM-CSF) [43].

Analytical, diagnostic and therapeutic context of EPO


  1. Absence of polycythemia in a child with a unique erythropoietin receptor mutation in a family with autosomal dominant primary polycythemia. Kralovics, R., Sokol, L., Prchal, J.T. J. Clin. Invest. (1998) [Pubmed]
  2. Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Celik, M., Gökmen, N., Erbayraktar, S., Akhisaroglu, M., Konakc, S., Ulukus, C., Genc, S., Genc, K., Sagiroglu, E., Cerami, A., Brines, M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. Human hematopoietic progenitors express erythropoietin. Stopka, T., Zivny, J.H., Stopkova, P., Prchal, J.F., Prchal, J.T. Blood (1998) [Pubmed]
  4. Hypoxia-inducible erythropoietin gene expression in human neuroblastoma cells. Stolze, I., Berchner-Pfannschmidt, U., Freitag, P., Wotzlaw, C., Rössler, J., Frede, S., Acker, H., Fandrey, J. Blood (2002) [Pubmed]
  5. Erythropoietin induces tyrosine phosphorylation and kinase activity of the c-fps/fes proto-oncogene product in human erythropoietin-responsive cells. Hanazono, Y., Chiba, S., Sasaki, K., Mano, H., Yazaki, Y., Hirai, H. Blood (1993) [Pubmed]
  6. Erythropoietin receptor expression and correlation to tamoxifen response and prognosis in breast cancer. Larsson, A.M., Jirström, K., Fredlund, E., Nilsson, S., Rydén, L., Landberg, G., Påhlman, S. Clin. Cancer Res. (2009) [Pubmed]
  7. Hepatic erythropoietin gene regulation by GATA-4. Dame, C., Sola, M.C., Lim, K.C., Leach, K.M., Fandrey, J., Ma, Y., Knöpfle, G., Engel, J.D., Bungert, J. J. Biol. Chem. (2004) [Pubmed]
  8. Does the use of erythropoietin reduce the risk of exposure to allogeneic blood transfusion in cardiac surgery? A systematic review and meta-analysis. Alghamdi, A.A., Albanna, M.J., Guru, V., Brister, S.J. Journal of cardiac surgery. (2006) [Pubmed]
  9. Erythropoietin in human milk: physiology and role in infant health. Semba, R.D., Juul, S.E. Journal of human lactation : official journal of International Lactation Consultant Association. (2002) [Pubmed]
  10. Update on erythropoietin treatment: should hemoglobin be normalized in patients with chronic kidney disease? Paoletti, E., Cannella, G. J. Am. Soc. Nephrol. (2006) [Pubmed]
  11. Erythrocyte PAF-acetylhydrolase activity in various stages of chronic kidney disease: effect of long-term therapy with erythropoietin. Papavasiliou, E.C., Gouva, C., Siamopoulos, K.C., Tselepis, A.D. Kidney Int. (2005) [Pubmed]
  12. Free radicals in the physiological control of cell function. Dröge, W. Physiol. Rev. (2002) [Pubmed]
  13. Epoetin for severe anemia in hepatoerythropoietic porphyria. Horina, J.H., Wolf, P. N. Engl. J. Med. (2000) [Pubmed]
  14. Erythropoietin for end-stage renal disease. Adamson, J.W., Eschbach, J.W. N. Engl. J. Med. (1998) [Pubmed]
  15. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. Besarab, A., Bolton, W.K., Browne, J.K., Egrie, J.C., Nissenson, A.R., Okamoto, D.M., Schwab, S.J., Goodkin, D.A. N. Engl. J. Med. (1998) [Pubmed]
  16. Expression of Bcl-x in erythroid precursors from patients with polycythemia vera. Silva, M., Richard, C., Benito, A., Sanz, C., Olalla, I., Fernández-Luna, J.L. N. Engl. J. Med. (1998) [Pubmed]
  17. Erythropoietin fails to interfere with the antiproliferative and cytotoxic effects of antitumor drugs. Gewirtz, D.A., Di, X., Walker, T.D., Sawyer, S.T. Clin. Cancer Res. (2006) [Pubmed]
  18. Mersalyl is a novel inducer of vascular endothelial growth factor gene expression and hypoxia-inducible factor 1 activity. Agani, F., Semenza, G.L. Mol. Pharmacol. (1998) [Pubmed]
  19. Human recombinant erythropoietin directly stimulates B cell immunoglobulin production and proliferation in serum-free medium. Kimata, H., Yoshida, A., Ishioka, C., Masuda, S., Sasaki, R., Mikawa, H. Clin. Exp. Immunol. (1991) [Pubmed]
  20. Neuroprotective properties of epoetin alfa. Cerami, A., Brines, M., Ghezzi, P., Cerami, C., Itri, L.M. Nephrol. Dial. Transplant. (2002) [Pubmed]
  21. Improved multilineage response of hematopoiesis in patients with myelodysplastic syndromes to a combination therapy with all-trans-retinoic acid, granulocyte colony-stimulating factor, erythropoietin and alpha-tocopherol. Ganser, A., Maurer, A., Contzen, C., Seipelt, G., Ottmann, O.G., Schadeck-Gressel, C., Kolbe, K., Haas, R., Zander, C., Reutzel, R., Hoelzer, D. Ann. Hematol. (1996) [Pubmed]
  22. Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation. Livnah, O., Stura, E.A., Middleton, S.A., Johnson, D.L., Jolliffe, L.K., Wilson, I.A. Science (1999) [Pubmed]
  23. Erythroid progenitors differentiate and mature in response to endogenous erythropoietin. Sato, T., Maekawa, T., Watanabe, S., Tsuji, K., Nakahata, T. J. Clin. Invest. (2000) [Pubmed]
  24. Characterization of endogenous cytokine concentrations after high-dose chemotherapy with autologous bone marrow support. Rabinowitz, J., Petros, W.P., Stuart, A.R., Peters, W.P. Blood (1993) [Pubmed]
  25. Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid progenitors. van den Akker, E., van Dijk, T., Parren-van Amelsvoort, M., Grossmann, K.S., Schaeper, U., Toney-Earley, K., Waltz, S.E., Löwenberg, B., von Lindern, M. Blood (2004) [Pubmed]
  26. Prostaglandin-E2 enhances EPO-mediated STAT5 transcriptional activity by serine phosphorylation of CREB. Boer, A.K., Drayer, A.L., Rui, H., Vellenga, E. Blood (2002) [Pubmed]
  27. A novel function of Stat1 and Stat3 proteins in erythropoietin-induced erythroid differentiation of a human leukemia cell line. Kirito, K., Uchida, M., Takatoku, M., Nakajima, K., Hirano, T., Miura, Y., Komatsu, N. Blood (1998) [Pubmed]
  28. Erythropoietin and hypoxia stimulate erythropoietin receptor and nitric oxide production by endothelial cells. Beleslin-Cokic, B.B., Cokic, V.P., Yu, X., Weksler, B.B., Schechter, A.N., Noguchi, C.T. Blood (2004) [Pubmed]
  29. Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds. Galeano, M., Altavilla, D., Bitto, A., Minutoli, L., Calò, M., Cascio, P.L., Polito, F., Giugliano, G., Squadrito, G., Mioni, C., Giuliani, D., Venuti, F.S., Squadrito, F. Crit. Care Med. (2006) [Pubmed]
  30. Biology of erythropoietin. Lacombe, C., Mayeux, P. Haematologica (1998) [Pubmed]
  31. The cytokine receptor gp130: faithfully promiscuous. Müller-Newen, G. Sci. STKE (2003) [Pubmed]
  32. Erythropoietin: physiology and pharmacology update. Fisher, J.W. Exp. Biol. Med. (Maywood) (2003) [Pubmed]
  33. Roles of Brahma and Brahma/SWI2-related gene 1 in hypoxic induction of the erythropoietin gene. Wang, F., Zhang, R., Beischlag, T.V., Muchardt, C., Yaniv, M., Hankinson, O. J. Biol. Chem. (2004) [Pubmed]
  34. Expression of the erythropoietin receptor by trophoblast cellsin the human placenta. Fairchild Benyo, D., Conrad, K.P. Biol. Reprod. (1999) [Pubmed]
  35. Erythropoietin induces the tyrosine phosphorylation of insulin receptor substrate-2. An alternate pathway for erythropoietin-induced phosphatidylinositol 3-kinase activation. Verdier, F., Chrétien, S., Billat, C., Gisselbrecht, S., Lacombe, C., Mayeux, P. J. Biol. Chem. (1997) [Pubmed]
  36. Involvement of the Src kinase Lyn in phospholipase C-gamma 2 phosphorylation and phosphatidylinositol 3-kinase activation in Epo signalling. Boudot, C., Dassé, E., Lambert, E., Kadri, Z., Mayeux, P., Chrétien, S., Haye, B., Billat, C., Petitfrère, E. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  37. Erythropoietin induces p21ras activation and p120GAP tyrosine phosphorylation in human erythroleukemia cells. Torti, M., Marti, K.B., Altschuler, D., Yamamoto, K., Lapetina, E.G. J. Biol. Chem. (1992) [Pubmed]
  38. Effect of inflammatory cytokines on hypoxia-induced erythropoietin production. Faquin, W.C., Schneider, T.J., Goldberg, M.A. Blood (1992) [Pubmed]
  39. Erythropoietin induces the tyrosine phosphorylation of GAB1 and its association with SHC, SHP2, SHIP, and phosphatidylinositol 3-kinase. Lecoq-Lafon, C., Verdier, F., Fichelson, S., Chrétien, S., Gisselbrecht, S., Lacombe, C., Mayeux, P. Blood (1999) [Pubmed]
  40. Evidence against a major role for Ca2+ in hypoxia-induced gene expression in human hepatoma cells (Hep3B). Metzen, E., Fandrey, J., Jelkmann, W. J. Physiol. (Lond.) (1999) [Pubmed]
  41. Interleukin 2 and erythropoietin activate STAT5/MGF via distinct pathways. Wakao, H., Harada, N., Kitamura, T., Mui, A.L., Miyajima, A. EMBO J. (1995) [Pubmed]
  42. An essential role for p300/CBP in the cellular response to hypoxia. Arany, Z., Huang, L.E., Eckner, R., Bhattacharya, S., Jiang, C., Goldberg, M.A., Bunn, H.F., Livingston, D.M. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  43. Mast cell growth factor (c-kit ligand) supports the growth of human multipotential progenitor cells with a high replating potential. Carow, C.E., Hangoc, G., Cooper, S.H., Williams, D.E., Broxmeyer, H.E. Blood (1991) [Pubmed]
  44. NADPH-cytochrome P-450 reductase in the plasma membrane modulates the activation of hypoxia-inducible factor 1. Osada, M., Imaoka, S., Sugimoto, T., Hiroi, T., Funae, Y. J. Biol. Chem. (2002) [Pubmed]
  45. Erythropoietin-mediated activation of JAK-STAT signaling contributes to cellular invasion in head and neck squamous cell carcinoma. Lai, S.Y., Childs, E.E., Xi, S., Coppelli, F.M., Gooding, W.E., Wells, A., Ferris, R.L., Grandis, J.R. Oncogene (2005) [Pubmed]
  46. Mechanisms of erythropoietin-induced brain protection in neonatal hypoxia-ischemia rat model. Sun, Y., Zhou, C., Polk, P., Nanda, A., Zhang, J.H. J. Cereb. Blood Flow Metab. (2004) [Pubmed]
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