TPA response element

TPA-responsive element tyrosine receptor kinase A 12-0-tetradecanoylphorbol- 13-acetate sixth letter in the Hebrew alphabet zeta-associated protein 70... 

Recent studies have demonstrated that lithium (and to a lesser extent VPA) produces, at therapeutically relevant concentrations, complex alterations in basal and/or stimulated DNA-binding of 12-o-tetradecanoyl-phorbol 13-acetate (TPA) response element (TRE) to AP-1 transcription factors. These alterations are produced not only in human SH-SY5Y cells in vitro, but also in rodent brain following chronic, in vivo administration [5, 7, 15-21]. Corresponding to an increase in basal AP-1 DNA-binding activity, lithium and VPA have been shown to increase the expression of a luciferase reporter gene driven by an SV40 promoter that contains TREs in a time- and concentration-dependent fashion. Mutations in the TRE... 

TPA responsive element (TRE)] and increases their expression. FOS is overexpressed in the majority of human osteosarcomas, while JUN is overexpressed in some lung cancers. In Burkitt s lymphoma, the transcription factor MYC is translocated and inserted near an immunoglobulin locus, where it falls under the regulation of an immunoglobulin promoter (Figure 24.18). This results in constitutive expression of high levels of MYC. In addition, various members of the MYC family are amplified in a variety of human and rodent tumors. 

Protein kinase C isozymes are activated by Euphorbiaceae plant-derived phorbol esters such as tetradecanoylphorbolacetate (TPA) that bind to the DAG-activation site. PKC can phosphorylate specific TFs that bind to DNA regulatory promoters called TPA response elements (TREs). This interaction enables transcription of specific genes. This process can be summarized as follows signalling giving elevated Ca2+ — PKC activation —> TF phosphorylation — P-TF binding to TRE — specific gene transcription switched on — specific gene expression. 

AP-1 site. The binding site on DNA at which the transcription factor AP-1 binds, thereby altering the rate of transcription for the adjacent gene. AP-1 is actually a complex between c-fos protein and c-jun protein, or sometimes is just c-jun dimers. The AP-1 site consensus sequence is (C/G)TGACT(C/ A)A. Also known as the TPA-response element (TRE). [TPA is a phorbol ester, tetradecanoyl phor-bol acetate, which is a chemical tumor promoter. 

Yamauchi, M., Ogata, Y., Kim, R. H., Li, J. J., Freedman, L. P., Sodek, J. (1996) AP-1 regulation of the rat bone sialoprotein gene transcription is mediated through a TPA response element within a glucocorticoid response unit in the gene promoter. Matrix Biol. 15, 119-130. 

Abbreviations used in this review APL, acute promyelocytic leukaemia CEF, chick embryo fibroblasts CRABP, cellular retinoic acid-binding protein ODC, ornithine decarboxylase RA, retinoic acid RARE, retinoic acid responsive element RAR, retinoic acid receptor RXR, retinoid X receptor TEMPO, 2,2,6,6-tetramethylpiperidine Y-oxide TOC, tracheal organ culture TPA, 12-<2-tetradecanoylphorbol-13-acetate TTNN, 6-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-2-naphthanoic acid TTNPB, 4-((.Q-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthyl)propenyl)benzoic acid. 

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