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Gene Review

TDGF1P4  -  teratocarcinoma-derived growth factor 1...

Homo sapiens

Synonyms: CR-4, CRIPTO-4, TDGF4
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Disease relevance of TDGF4

  • We report here the effects of a novel tyrosine kinase inhibitor CR4 that interferes with growth-promoting pathways to markedly inhibit the growth and survival of both Philadelphia-positive and -negative acute lymphoblastic leukemia (ALL) as well as acute myeloid leukemia (AML) [1].
  • Recent studies from this laboratory have demonstrated that macrophage phagocytosis of virulent strains (Erdman and H37Rv), but not the attenuated H37Ra strain of Mycobacterium tuberculosis, is mediated by phagocyte mannose receptors (MR) in addition to complement receptors (CR1 and the leukocyte integrins CR3 and CR4) [2].
  • Glucocorticoids regulate the trafficking of mouse mammary tumor virus (MMTV) glycoproteins to the cell surface in the rat hepatoma cell line M1.54, but not in the immunoselected sorting variant CR4 [3].
  • Two effective ribozymes (CR2 and CR4) that target HCV RNA 5' UTR and capsid gene regions were generated [4].
  • It is concluded that CR4 may be useful in increasing hours on per day in subgroups of Parkinson's disease patients who have less severe fluctuations [5].

High impact information on TDGF4

  • Normal neutrophil and macrophage CR4-dependent EC3bi rosettes were inhibited by monoclonal anti-p150,95, and cells from a patient with CD18 deficiency did not form CR4-dependent EC3bi rosettes [6].
  • Neutrophil and monocyte cell surface p150,95 has iC3b-receptor (CR4) activity resembling CR3 [6].
  • While efficiently ablating leukemic cell growth, normal cell growth and differentiation remain unaffected by CR4 [1].
  • However, treatment of leukocytes with phorbol 12-myristate 13 acetate increased CR3 and CR4 expression on both myeloid cells and a lymphocyte subpopulation [7].
  • Eighteen patients in first complete remission (CR1), 36 in CR2, 16 in CR3, and four in CR4 were transplanted [8].

Chemical compound and disease context of TDGF4

  • The only significant difference in these parameters between the CR4 and standard Sinemet treatment periods in the entire group was a decrease in hours of dyskinesia per day [5].

Biological context of TDGF4

  • The three new sequences (TDGF2, TDGF4 and TDGF5) are truncated at the 5' end and have accumulated several point mutations, deletions and insertions [9].
  • These observations strongly suggest that alpha(Hr1) constitutes an integrin molecule on the hemocytes of H. roretzi that functions as an ancestral form of CR3 and CR4 and mediates phagocytosis in the primitive complement system of the ascidian [10].
  • Soluble CD16 bound to CR3 (CDllb/CD18)- and CR4 (CDllc/CD18)- positive leukocytes and cell lines, the labeling was inhibited by anti-CD11b, CD11c or CD18 mAbs, and the up-regulation of CR3 and CR4 led to an increased fixation of sCD16 [11].
  • Furthermore, binding of M. tuberculosis transduced a potent signal, resulting in tyrosine phosphorylation of macrophage proteins, which was in part mediated by CR4 [12].
  • Role of CR4 in Mycobacterium tuberculosis-human macrophages binding and signal transduction in the absence of serum [12].

Anatomical context of TDGF4


Associations of TDGF4 with chemical compounds

  • Overall benefit waned over the next 6 months, despite addition of standard levodopa or Sinemet to overcome the delayed onset of antiparkinsonian effect of CR4 which resulted from prolongation in the Tmax for levodopa [15].
  • The major benefits of CR4 were reduction in off time and in the number of daily off periods, with fewer levodopa doses per day and prolongation of the interdose interval [15].
  • Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies [16].
  • U937 cells differentiated with phorbol myristate acetate resembled AM phi in receptor expression but exhibited almost no CR4-dependent rosetting [17].
  • The change in C3 localization changed the mode of phagocytosis in macrophages, such that localizing C3 at the edge of the capsule allowed phagocytosis through C3-CR3 and C3-CR4 interactions, which did not occur in serum without Ab [18].

Physical interactions of TDGF4

  • E1A CR4 binds the CtBP corepressor, but the mechanism by which this modulates the frequency of transformation remains to be determined [19].

Other interactions of TDGF4

  • TDGF2, TDGF4 and TDGF6 map on Chrs 2q37, 6p25 and 3q22, respectively [9].
  • The CR4 and RPS12 transcripts are the size of unedited RNAs suggesting that they are processed [20].
  • The 3 year probability of disease-free survival (DFS) was influenced by disease stage at ABMT: CR1 48%, CR2 28%, CR3 plus CR4 15% [21].
  • Forty-eight subjects (group T) with primary T wave aberrations in their electrocardiograms (e.g. notches, flattening or inversion in leads II, CR4 and CR7 but without a concomitant ST depression) and 38 controls (group C), examined previously at the age of 18-19 years, were re-examined after 5.4 and 7.5 years respectively [22].

Analytical, diagnostic and therapeutic context of TDGF4

  • Immunofluorescence staining demonstrated patching and occasional capping of CR3, whereas CR4 remained uniformly distributed [17].
  • Ophthalmoscopy and retinal photography (Canon CR4 45NM) with mydriasis were all practice based [23].
  • Seventy-five patients, each of whom had > 1 mm ST-segment elevation on an intracoronary electrocardiogram from the myocardium distal to the stenosis during balloon occlusion, were studied for the occurrence of > or = 1 mm ST-segment elevation or depression on the simultaneously recorded Holter leads II, III, aVF, CM5, CR4, and inverse Nehb J [24].
  • To investigate the role played by ligation of complement receptors CR3 and CR4 in non-adherent neutrophils, we designed a novel assay system utilizing dual optical traps, respectively, holding a suspended unactivated cell and presenting a specific ligand-coated bead to the cell surface [25].


  1. Inhibition of acute lymphoblastic and myeloid leukemias by a novel kinase inhibitor. Grunberger, T., Demin, P., Rounova, O., Sharfe, N., Cimpean, L., Dadi, H., Freywald, A., Estrov, Z., Roifman, C.M. Blood (2003) [Pubmed]
  2. Binding of the terminal mannosyl units of lipoarabinomannan from a virulent strain of Mycobacterium tuberculosis to human macrophages. Schlesinger, L.S., Hull, S.R., Kaufman, T.M. J. Immunol. (1994) [Pubmed]
  3. Glucocorticoid-regulated and constitutive trafficking of proteolytically processed cell surface-associated glycoproteins in wild type and variant rat hepatoma cells. Amacher, S.L., Goodman, L.J., Bravo, D.A., Wong, K.Y., Goldfine, I.D., Hawley, D.M., Firestone, G.L. Mol. Endocrinol. (1989) [Pubmed]
  4. A potential therapeutic application of hairpin ribozymes: in vitro and in vivo studies of gene therapy for hepatitis C virus infection. Welch, P.J., Tritz, R., Yei, S., Leavitt, M., Yu, M., Barber, J. Gene Ther. (1996) [Pubmed]
  5. Efficacy of sinemet CR4 in subgroups of patients with Parkinson's disease. Factor, S.A., Sanchez-Ramos, J.R., Weiner, W.J., Ingenito, A.M. J. Neurol. Neurosurg. Psychiatr. (1989) [Pubmed]
  6. Neutrophil and monocyte cell surface p150,95 has iC3b-receptor (CR4) activity resembling CR3. Myones, B.L., Dalzell, J.G., Hogg, N., Ross, G.D. J. Clin. Invest. (1988) [Pubmed]
  7. Binding of fluorescein-labeled anaphylatoxin C5a to human peripheral blood, spleen, and bone marrow leukocytes. Werfel, T., Oppermann, M., Schulze, M., Krieger, G., Weber, M., Götze, O. Blood (1992) [Pubmed]
  8. Allogeneic bone marrow transplantation for patients with high-risk acute lymphoblastic leukemia. Wingard, J.R., Piantadosi, S., Santos, G.W., Saral, R., Vriesendorp, H.M., Yeager, A.M., Burns, W.H., Ambinder, R.F., Braine, H.G., Elfenbein, G. J. Clin. Oncol. (1990) [Pubmed]
  9. Assignment of human teratocarcinoma derived growth factor (TDGF) sequences to chromosomes 2q37, 3q22, 6p25 and 19q13.1. Scognamiglio, B., Baldassarre, G., Cassano, C., Tucci, M., Montuori, N., Dono, R., Lembo, G., Barra, A., Lago, C.T., Viglietto, G., Rocchi, M., Persico, M.G. Cytogenet. Cell Genet. (1999) [Pubmed]
  10. Cloning and characterization of integrin alpha subunits from the solitary ascidian, Halocynthia roretzi. Miyazawa, S., Azumi, K., Nonaka, M. J. Immunol. (2001) [Pubmed]
  11. Soluble Fcgamma receptor type III (FcgammaRIII, CD16) triggers cell activation through interaction with complement receptors. Galon, J., Gauchat, J.F., Mazières, N., Spagnoli, R., Storkus, W., Lötze, M., Bonnefoy, J.Y., Fridman, W.H., Sautès, C. J. Immunol. (1996) [Pubmed]
  12. Role of CR4 in Mycobacterium tuberculosis-human macrophages binding and signal transduction in the absence of serum. Zaffran, Y., Zhang, L., Ellner, J.J. Infect. Immun. (1998) [Pubmed]
  13. Complement and the recruitment of mononuclear osteoclasts. Mangham, D.C., Scoones, D.J., Drayson, M.T. J. Clin. Pathol. (1993) [Pubmed]
  14. Complement receptors in neutrophils. Sengeløv, H. Crit. Rev. Immunol. (1995) [Pubmed]
  15. Controlled-release levodopa/carbidopa. II. Sinemet CR4 treatment of response fluctuations in Parkinson's disease. Cedarbaum, J.M., Breck, L., Kutt, H., McDowell, F.H. Neurology (1987) [Pubmed]
  16. Controlled-release carbidopa/levodopa (Sinemet 50/200 CR4): clinical and pharmacokinetic studies. LeWitt, P.A., Nelson, M.V., Berchou, R.C., Galloway, M.P., Kesaree, N., Kareti, D., Schlick, P. Neurology (1989) [Pubmed]
  17. Macrophage cytoskeleton association with CR3 and CR4 regulates receptor mobility and phagocytosis of iC3b-opsonized erythrocytes. Ross, G.D., Reed, W., Dalzell, J.G., Becker, S.E., Hogg, N. J. Leukoc. Biol. (1992) [Pubmed]
  18. Monoclonal antibodies can affect complement deposition on the capsule of the pathogenic fungus Cryptococcus neoformans by both classical pathway activation and steric hindrance. Zaragoza, O., Casadevall, A. Cell. Microbiol. (2006) [Pubmed]
  19. Recent lessons in gene expression, cell cycle control, and cell biology from adenovirus. Berk, A.J. Oncogene (2005) [Pubmed]
  20. Mitochondrial transcripts are processed but are not edited normally in Trypanosoma equiperdum (ATCC 30019) which has kDNA sequence deletion and duplication. Shu, H.H., Stuart, K. Nucleic Acids Res. (1994) [Pubmed]
  21. Autologous bone marrow transplantation for acute leukemia: results and prognostic factors in 90 consecutive patients. Sierra, J., Grañena, A., García, J., Valls, A., Carreras, E., Rovira, M., Canals, C., Martínez, E., Puntí, C., Algara, M. Bone Marrow Transplant. (1993) [Pubmed]
  22. A 5-year follow-up of young men with primary T wave aberrations in their electrocardiograms. Atterhög, J.H. Acta medica Scandinavica. (1981) [Pubmed]
  23. Screening for diabetic retinopathy by general practitioners: ophthalmoscopy or retinal photography as 35 mm colour transparencies? Owens, D.R., Gibbins, R.L., Lewis, P.A., Wall, S., Allen, J.C., Morton, R. Diabet. Med. (1998) [Pubmed]
  24. The inverse Nehb J lead increases the sensitivity of Holter electrocardiographic monitoring for detecting myocardial ischemia. Seeberger, M.D., Moerlen, J., Skarvan, K., Friedli, D., Vankova, S., Buser, P., Pfisterer, M. Am. J. Cardiol. (1997) [Pubmed]
  25. Interaction of non-adherent suspended neutrophils to complement opsonized pathogens: a new assay using optical traps. Suzuki, T., Yanai, M., Kubo, H., Kanda, A., Sasaki, H., Butler, J.P. Cell Res. (2006) [Pubmed]
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