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Gene Review

TMPO  -  thymopoietin

Homo sapiens

Synonyms: CMD1T, LAP2, LEMD4, PRO0868, TP
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Disease relevance of TMPO


High impact information on TMPO

  • Differentiation of lymphoid precursor cells in a variety of species is induced by polypeptide hormones such as thymopoietin for T cells and bursin for B cells [6].
  • These inducing properties of bursin are the reverse of the inducing properties of thymopoietin produced by the thymus and are appropriate to a physiological B-cell-inducing hormone [6].
  • HA95-LAP2 beta interaction is not required for NE formation [7].
  • We propose that an interaction of LAP2beta, or LAP2 proteins, with HA95 is involved in the control of initiation of DNA replication [7].
  • Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA [8].

Chemical compound and disease context of TMPO


Biological context of TMPO


Anatomical context of TMPO

  • TMPO alpha is present diffusely throughout the nucleus, while TMPOs beta and gamma are localized to the nuclear membrane [12].
  • Here we report on the demonstration of putative human TMPOdelta and epsilon by immunoblotting of human cell lines using a newly prepared polyclonal antiserum against the common N-terminal region of TMPO [16].
  • At least three LAP2 isoforms are identified in normal and neoplastic thyroid [17].
  • Since the lamin-binding fragment of LAP2 most likely acts by inhibiting dynamics of the nuclear lamina, our results suggest that a normal function of LAP2 involves regulation of nuclear lamina growth [15].
  • Thymopoietin (TP) was originally isolated as a 5-kDa 49-aa protein from bovine thymus in studies of the effects of thymic extracts on neuromuscular transmission and was subsequently observed to affect T-cell differentiation and function [18].

Associations of TMPO with chemical compounds

  • Analogous experiments with 3,3,5,5-tetramethyl-1-pyrroline N-oxide (TMPO) led only to the trapping of alkoxyl radicals with no evidence for peroxyl radical adducts, this is presumably due to a decreased rate of radical addition because of increased steric hindrance [19].
  • (C5Me5)3Sm reacts with the free radical 2,2,6,6-tetramethylpiperidinyl-1-oxy (TMPO) to form (C5Me5)2 and the per nitroxide [(eta 1-ONC5H6Me4)2Sm(mu-eta 1:eta 2-ONC5H6Me4)]2 [20].
  • The effect of myoglobin on the stability of the hydroxyl-radical adducts of 5,5 dimethyl-1-pyrolline-N-oxide (DMPO), 3,3,5,5 tetramethyl-1-pyrolline-N-oxide (TMPO) and 1-alpha-phenyl-tert-butyl nitrone (PBN) in the presence of hydrogen peroxide [21].
  • Hydrogen peroxide readily converts myoglobin to its ferryl (FeIV) derivative, and this centre may be responsible for the oxidation of the DMPO and TMPO adducts [21].
  • In contrast, we found that the portion of LAP2 involved in binding to chromosomes resides in a separate region of the protein near its NH2 terminus [22].

Physical interactions of TMPO


Regulatory relationships of TMPO


Other interactions of TMPO


Analytical, diagnostic and therapeutic context of TMPO


  1. Results in two infants with the DiGeorge syndrome--effects of long-term TP5. Businco, L., Rubaltelli, F.F., Paganelli, R., Galli, E., Ensoli, B., Betti, P., Aiuti, F. Clin. Immunol. Immunopathol. (1986) [Pubmed]
  2. Effect of thymopoietin and interleukin 2 on depressed mitogenic responsiveness and colony formation of lymphocytes from patients with preleukemia. Knox, S.J., Rosenblatt, L.S., Anderson, R.W., Greenberg, B.R. Thymus (1986) [Pubmed]
  3. Directed vascular expression of the thromboxane A2 receptor results in intrauterine growth retardation. Rocca, B., Loeb, A.L., Strauss, J.F., Vezza, R., Habib, A., Li, H., FitzGerald, G.A. Nat. Med. (2000) [Pubmed]
  4. Involvement of a high-mobility-group protein in the transcriptional activity of herpes simplex virus latency-active promoter 2. French, S.W., Schmidt, M.C., Glorioso, J.C. Mol. Cell. Biol. (1996) [Pubmed]
  5. Myasthenic sera recognize the human acetylcholine receptor bound to thymopoietin. Morel, E., Vernet-der Garabedian, B., Raimond, F., Audhya, T.K., Goldstein, G., Bach, J.F. Eur. J. Immunol. (1987) [Pubmed]
  6. Tripeptide structure of bursin, a selective B-cell-differentiating hormone of the bursa of fabricius. Audhya, T., Kroon, D., Heavner, G., Viamontes, G., Goldstein, G. Science (1986) [Pubmed]
  7. HA95 and LAP2 beta mediate a novel chromatin-nuclear envelope interaction implicated in initiation of DNA replication. Martins, S., Eikvar, S., Furukawa, K., Collas, P. J. Cell Biol. (2003) [Pubmed]
  8. Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA. Cai, M., Huang, Y., Ghirlando, R., Wilson, K.L., Craigie, R., Clore, G.M. EMBO J. (2001) [Pubmed]
  9. Differential expression of platelet-derived endothelial cell growth factor/thymidine phosphorylase in human lung carcinoma cell lines. Heldin, N.E., Usuki, K., Bergh, J., Westermark, B., Heldin, C.H. Br. J. Cancer (1993) [Pubmed]
  10. Treatment of cutaneous T-cell lymphomas with TP-5. Evaluation of the clinical effect in 8 patients. Przybilla, B., Burg, G., Schmoeckel, C., Braun-Falco, O. Acta Derm. Venereol. (1983) [Pubmed]
  11. Different pathways for activation of extracellular signal-regulated kinase through thromboxane A2 receptor isoforms. Miyosawa, K., Sasaki, M., Ohkubo, S., Nakahata, N. Biol. Pharm. Bull. (2006) [Pubmed]
  12. Structure and mapping of the human thymopoietin (TMPO) gene and relationship of human TMPO beta to rat lamin-associated polypeptide 2. Harris, C.A., Andryuk, P.J., Cline, S.W., Mathew, S., Siekierka, J.J., Goldstein, G. Genomics (1995) [Pubmed]
  13. Genomic structure and expression of parathyroid hormone-related protein gene (PTHrP) in a teleost, Fugu rubripes. Power, D.M., Ingleton, P.M., Flanagan, J., Canario, A.V., Danks, J., Elgar, G., Clark, M.S. Gene (2000) [Pubmed]
  14. Isolation and complete amino acid sequence of human thymopoietin and splenin. Goldstein, G., Schlesinger, D.H., Audhya, T. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  15. Lamin-binding fragment of LAP2 inhibits increase in nuclear volume during the cell cycle and progression into S phase. Yang, L., Guan, T., Gerace, L. J. Cell Biol. (1997) [Pubmed]
  16. On the role of thymopoietins in cell proliferation. Immunochemical evidence for new members of the human thymopoietin family. Weber, P.J., Eckhard, C.P., Gonser, S., Otto, H., Folkers, G., Beck-Sickinger, A.G. Biol. Chem. (1999) [Pubmed]
  17. Nuclear envelope organization in papillary thyroid carcinoma. Fischer, A.H., Taysavang, P., Weber, C.J., Wilson, K.L. Histol. Histopathol. (2001) [Pubmed]
  18. Three distinct human thymopoietins are derived from alternatively spliced mRNAs. Harris, C.A., Andryuk, P.J., Cline, S., Chan, H.K., Natarajan, A., Siekierka, J.J., Goldstein, G. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  19. Studies on the photolytic breakdown of hydroperoxides and peroxidized fatty acids by using electron spin resonance spectroscopy. Spin trapping of alkoxyl and peroxyl radicals in organic solvents. Davies, M.J., Slater, T.F. Biochem. J. (1986) [Pubmed]
  20. The tetramethylpiperidinyl-1-oxide anion (TMPO-) as a ligand in lanthanide chemistry: synthesis of the per(TMPO-) complex [(ONC5H6Me4)2Sm(mu-ONC5H6Me4)]2. Evans, W.J., Perotti, J.M., Doedens, R.J., Ziller, J.W. Chem. Commun. (Camb.) (2001) [Pubmed]
  21. The effect of myoglobin on the stability of the hydroxyl-radical adducts of 5,5 dimethyl-1-pyrolline-N-oxide (DMPO), 3,3,5,5 tetramethyl-1-pyrolline-N-oxide (TMPO) and 1-alpha-phenyl-tert-butyl nitrone (PBN) in the presence of hydrogen peroxide. De Bono, D., Yang, W.D., Symons, M.C. Free Radic. Res. (1994) [Pubmed]
  22. The major nuclear envelope targeting domain of LAP2 coincides with its lamin binding region but is distinct from its chromatin interaction domain. Furukawa, K., Fritze, C.E., Gerace, L. J. Biol. Chem. (1998) [Pubmed]
  23. Caspase-dependent proteolysis of integral and peripheral proteins of nuclear membranes and nuclear pore complex proteins during apoptosis. Buendia, B., Santa-Maria, A., Courvalin, J.C. J. Cell. Sci. (1999) [Pubmed]
  24. Domain-specific disassembly and reassembly of nuclear membranes during mitosis. Buendia, B., Courvalin, J.C. Exp. Cell Res. (1997) [Pubmed]
  25. Thymopoietin (lamina-associated polypeptide 2) gene mutation associated with dilated cardiomyopathy. Taylor, M.R., Slavov, D., Gajewski, A., Vlcek, S., Ku, L., Fain, P.R., Carniel, E., Di Lenarda, A., Sinagra, G., Boucek, M.M., Cavanaugh, J., Graw, S.L., Ruegg, P., Feiger, J., Zhu, X., Ferguson, D.A., Bristow, M.R., Gotzmann, J., Foisner, R., Mestroni, L. Hum. Mutat. (2005) [Pubmed]
  26. Demonstration of abnormalities in expression of thymic epithelial surface antigens in severe cellular immunodeficiency diseases. Haynes, B.F., Warren, R.W., Buckley, R.H., McClure, J.E., Goldstein, A.L., Henderson, F.W., Hensley, L.L., Eisenbarth, G.S. J. Immunol. (1983) [Pubmed]
  27. Bioassay determinations of thymopoietin and thymic hormone levels in human plasma. Twomey, J.J., Goldstein, G., Lewis, V.M., Bealmear, P.M., Good, R.A. Proc. Natl. Acad. Sci. U.S.A. (1977) [Pubmed]
  28. Immunoassay for bovine serum thymopoietin: discrimination from splenin by monoclonal antibodies. Fuccello, A., Audhya, T., Talle, M.A., Goldstein, G. Arch. Biochem. Biophys. (1984) [Pubmed]
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