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Gene Review

Tgm4  -  transglutaminase 4

Rattus norvegicus

Synonyms: DP1, Dorsal prostate transglutaminase, Dorsal protein 1, Dp1, Protein-glutamine gamma-glutamyltransferase 4, ...
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Disease relevance of Tgm4

  • Recombinant DP1 cDNA clones were identified from a bacteriophage lambda gt11 rat coagulating gland expression library using an affinity purified polyclonal antibody [1].
  • In contrast, an induction of E2F-1, 3, and 4 and the DP-1 protein was observed during the development of myocyte hypertrophy in neonatal myocytes treated with serum or phenylephrine, whereas the protein levels of E2F-5 were decreased with serum stimulation [2].

High impact information on Tgm4

  • Treatment for 1 week with a selective COX-2 inhibitor or with a selective PGD2 receptor (DP1) antagonist significantly reduced susceptibility of postcolitis rats to aberrant crypt foci development, beta-catenin expression, and mucosal thickness [3].
  • Fast atom bombardment mapping and automated Edman degradation experiments allowed us to verify that at least 85% of the entire transglutaminase amino acid sequence is identical to that derived from the cDNA of the major androgen-dependent rat prostate protein called DP1 [4].
  • Molecular cloning of rat prostate transglutaminase complementary DNA. The major androgen-regulated protein DP1 of rat dorsal prostate and coagulating gland [1].
  • In DRTF1/E2F the activity of DP-1 is under cell cycle control, possibly by phosphorylation, and in many types of cells it is a frequent, if not general DNA binding component of DRTF1/E2F [5].
  • Thus, activated Ha-ras can co-operate with DP-1 or DP-2 in the transformation of rat embryo fibroblasts, establishing for the first time that DP proteins are endowed with proto-oncogenic activity [5].

Biological context of Tgm4

  • Amino acid sequence deduced from DNA contained sequences identical with several DP1 cyanogen bromide cleavage fragments [1].
  • Here, we show that DP-1 and DP-2 are integrated with another growth regulating pathway which involves signal transduction emanating from activated Ras protein [5].
  • Ventral lobe mRNA was hybridized with a prostate binding protein (PBP) cDNA probe, while lateral and dorsal mRNA were hybridized with RWB (seminal vesicle secretory protein or SVS-II), probasin, and DP1 cDNA probes [6].
  • Here we investigated the role of E2F1 and E2F4 expression, with or without co-expression of DP1 or DP2, on cell proliferation in transiently transfected primary rat MCs [7].
  • Moreover, introduction of constitutively active pRb and transcriptionally inert mutant E2F1/DP1 efficiently protected cardiomyocytes from apoptosis [8].

Anatomical context of Tgm4

  • Thus, mRNA and protein levels of E2F-1, 3, and 4 and DP-1 and DP-2 were down-regulated during development to undetectable levels in adult myocytes [2].
  • In this study, we examined the function of PGD(2) and its two receptors DP1 and chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2) (DP2) in neuronal survival [9].
  • Similar results were obtained for four additional androgen-regulated prostatic mRNAs (prostatic binding protein [PBP], Royal Winnipeg Ballet [RWB], probasin, and dorsal protein-1 [DP-1]), all of which are markers of a differentiated ductal epithelium [10].
  • Dorsal protein-1 and probasin expressions of epithelial cells in this coculture system were the same as in rat prostate in vivo [11].

Associations of Tgm4 with chemical compounds

  • Expression of DP1 mRNA was androgen-dependent, decreasing approximately 80% 7 days after castration and increasing rapidly following androgen replacement [1].
  • It signals through two distinct G protein-coupled receptors, DP1 and DP2, that have opposing effects on cyclic AMP (cAMP) production [9].
  • These studies indicate that activation of the PGD(2) DP1 receptor protects against excitotoxic injury in a cAMP-dependent manner, consistent with recent studies of PGE(2) receptors that also suggest a neuroprotective effect of prostaglandin receptors [9].
  • This effect was mimicked by the DP1-selective agonist BW245C but not by the PGD(2) metabolite 15d-PGJ(2), suggesting that neuroprotection was mediated by the DP1 receptor [9].

Analytical, diagnostic and therapeutic context of Tgm4

  • Complementary DNA (cDNA) that codes for a major androgen-dependent secretory protein of rat coagulating gland and dorsal prostate, dorsal protein 1 (DP1), was isolated by molecular cloning [1].
  • Southern blot analysis of restriction enzyme-digested rat DNA indicated that DP1 is encoded by a single gene and that no major genomic rearrangements accounted for its lack of expression in the dorsal prostate-derived rat Dunning tumor [1].
  • On Northern blots, DP1 message significantly declined, probasin mRNA was modestly suppressed, and RWB expression was significantly elevated compared to those in control tissue [6].
  • Epithelial cell differentiation was evaluated with the reconstruction of acinus-like structures and with immunohistochemistry of rat dorsal prostate-specific proteins, dorsal protein-1 and probasin [11].


  1. Molecular cloning of rat prostate transglutaminase complementary DNA. The major androgen-regulated protein DP1 of rat dorsal prostate and coagulating gland. Ho, K.C., Quarmby, V.E., French, F.S., Wilson, E.M. J. Biol. Chem. (1992) [Pubmed]
  2. Inhibition of E2F abrogates the development of cardiac myocyte hypertrophy. Vara, D., Bicknell, K.A., Coxon, C.H., Brooks, G. J. Biol. Chem. (2003) [Pubmed]
  3. Predisposition to colorectal cancer in rats with resolved colitis: role of cyclooxygenase-2-derived prostaglandin d2. Zamuner, S.R., Bak, A.W., Devchand, P.R., Wallace, J.L. Am. J. Pathol. (2005) [Pubmed]
  4. Transglutaminase from rat coagulating gland secretion. Post-translational modifications and activation by phosphatidic acids. Esposito, C., Pucci, P., Amoresano, A., Marino, G., Cozzolino, A., Porta, R. J. Biol. Chem. (1996) [Pubmed]
  5. Proto-oncogenic properties of the DP family of proteins. Jooss, K., Lam, E.W., Bybee, A., Girling, R., Müller, R., La Thangue, N.B. Oncogene (1995) [Pubmed]
  6. Effects of neonatal estrogen exposure on prostatic secretory genes and their correlation with androgen receptor expression in the separate prostate lobes of the adult rat. Prins, G.S., Woodham, C., Lepinske, M., Birch, L. Endocrinology (1993) [Pubmed]
  7. Inhibitory effects of novel E2F decoy oligodeoxynucleotides on mesangial cell proliferation by coexpression of E2F/DP. Park, K.K., Deok Ahn, J., Lee, I.K., Magae, J., Heintz, N.H., Kwak, J.Y., Lee, Y.C., Cho, Y.S., Kim, H.C., Chae, Y.M., Ho Kim, Y., Kim, C.H., Chang, Y.C. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  8. Inhibition of hypoxia-induced apoptosis by modulation of retinoblastoma protein-dependent signaling in cardiomyocytes. Hauck, L., Hansmann, G., Dietz, R., von Harsdorf, R. Circ. Res. (2002) [Pubmed]
  9. Prostaglandin D2 mediates neuronal protection via the DP1 receptor. Liang, X., Wu, L., Hand, T., Andreasson, K. J. Neurochem. (2005) [Pubmed]
  10. In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs prostate development. 1. Effects on gene expression. Roman, B.L., Peterson, R.E. Toxicol. Appl. Pharmacol. (1998) [Pubmed]
  11. Proliferation and differentiation of rat dorsal prostatic epithelial cells in collagen gel matrix culture, focusing upon effects of adipocytes. Tokuda, Y., Toda, S., Masaki, Z., Sugihara, H. International journal of urology : official journal of the Japanese Urological Association. (1999) [Pubmed]
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