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].

References