Disease relevance of TRNAE1

• A number of diseases have been attributed to TRE, including Huntington disease and myotonic dystrophy (DM), but attempts at genetic therapy have yet to prove successful [1].
• The function of the nTRE depended on its location in the 3'-UT/FR; it was inactive when positioned down-stream of the simian virus 40 (SV40) 3'-UT/FR, and it acted as a positive TRE when placed upstream of the hGH promoter [2].
• These findings suggest that estradiol modulates expression of the human alpha subunit gene in pituitary and choriocarcinoma cells by direct binding of ER to the alpha gene promoter, and that interaction of ER with the alpha gene negative TRE accounts for the antagonistic effects of estradiol and T3 [3].
• The human T-cell leukemia virus type I (HTLV-I) promoter contains three copies of imperfect repeats of a 21-base pair sequence designated here as TRE (Tax-response element) that is responsive to the virally encoded transactivator protein Tax [4].
• The addition of tetracycline in 293 cells blocks the binding of tTA to TRE and substantially inhibits GFP-Bax expression and toxicity, thus allowing the packaging and production of Ad/gBax [5].

High impact information on TRNAE1

• A group I intron ribozyme (DMPK-RZ1) was designed to modify the TRE at the 3' end of the human myotonic dystrophy protein kinase (DMPK) transcripts [1].
• Binding of the human transcription factor Jun/AP-1 to a conserved 8 bp nucleotide sequence (TRE) is responsible for increased transcription of different cellular genes in response to tumor promoters, such as TPA, and serum factors [6].
• Transcription induced by ligand-activated RAR-epsilon from a TRE can, however, be repressed by thyroid-hormone receptor in the absence of its ligand [7].
• Specific amino-acid substitutions in this basic, presumably alpha-helical, region abolish the interaction of Fos/Jun with the TRE but not the association of the two proteins [8].
• The X2 box of MHC class II promoters is homologous to TRE/CRE elements and is required for expression of MHC class II genes [9].

Chemical compound and disease context of TRNAE1

• Mutant G345R showed a stronger dominant negative effect than did R316H when using a double palindromic TRE fused to herpes simplex thymidine kinase-Luc reporter as a positive TRE [10].
• Subcutaneous tumors in SCID mice that were implanted with MCF/TRE/tk/Tet-On cells shrank remarkably after Dox and GCV administration as compared with the control [11].

Biological context of TRNAE1

• When a reporter gene containing T3-responsive elements (TRE), TRE-pal2, DR4 or myosin heavy chain alpha subunit, was used, transcriptional activation induced by R338W was higher than that by K443E [12].
• Each TRE-like sequence has no activity by itself but acts synergistically to form a strong enhancer which is active even in the very low level of AP-1 activity in F9 cells [13].
• Homology searches of 1.5 kb of genomic DNA 5' of the coding region of the prestin gene allowed the identification of a thyroid hormone (TH) response element (TRE) in the first intron upstream of the prestin ATG codon [14].
• Coinjection of the dominant-negative Xenopus and human mutant TR beta s into Xenopus tadpole tails totally abolished the T3 responsiveness of the wt-xTR beta with different TREs, including the natural DR +4 TRE of the xTR beta promoter [15].
• Functional analysis of MCP-1 promoter and site-specific mutations indicates that the proximal tissue plasminogen activator-responsive element (TRE) in the -60-bp promoter region is sufficient for strain or H2O2 inducibility [16].

Anatomical context of TRNAE1

• Unlike other TRE-containing enhancers, GPEI exhibits a strong transcriptional enhancing activity in F9 embryonic stem cells [13].
• The ability of pX also to increase TRE-directed transcription in cell lines in which AP1-binding activity is not increased (i.e., HeLa, CV1, and PLC/PRF/5 cells) suggests that pX can activate canonical TRE sites by different mechanisms as well [17].
• Consistent with these data, the binding of 9-cis-RA to the bcr3-PML/RAR alpha product resulted in increased transcriptional activation of the RA-responsive element (RARE) TRE, but not of the betaRARE, in transiently transfected COS-1 cells [18].
• We suggest that the FAP oligonucleotide acts through a factor(s) distinct from those employed by the TRE and CRE and that the FAP-associated protein factor(s) may differ in HeLa and PC12 cells in expression or posttranslational regulation [19].
• In contrast to the results with TRE sites, both v-Jun and c-Jun activate transcription through the human T-cell leukemia virus type I 21-bp repeat which contains a sequence homologous to the cyclic AMP responsive element [20].

Associations of TRNAE1 with chemical compounds

• Chromosomal band 1p36 encodes genes for small nuclear RNA U1 (RNU-1) and for the tRNAs of glutamic acid (TRE) and asparagine (TRN) [21].
• A DNA element located at positions -295 to -289 of the c-fos promoter (FAP site) is highly homologous to a consensus 12-O-tetradecanoyl phorbol-13-acetate-responsive element (TRE) and to a cyclic AMP (cAMP)-responsive element (CRE) [19].
• U937 cells were cotransfected with a plasmid expressing the TR and a reporter plasmid containing a T3 response element (TRE) oriented either as a direct repeat or as a palindrome upstream of the thymidine kinase promoter linked to the chloramphenicol acetyltransferase gene [22].
• Furthermore, H-7 and staurosporine also inhibited the binding activity to TRE in the cells treated by the cytokine [23].
• When footprint A (-101 to -49) or 7 alpha TRE (-73 to -55) sequence was linked upstream to a heterologous SV40 promoter/luciferase plasmid and transiently transfected into HepG2 cells, taurodeoxycholate suppressed the SV40 promoter activity [24].

Physical interactions of TRNAE1

• AP-1 binding to the TRE promoter is regulated by the quantity, composition and post-translational modifications of proteins in the AP-1 complex [25].
• ICAM-TRE binding activity was induced within 30 min following TPA treatment [26].
• Thyroid hormone receptor beta (TRbeta) binds to an inverted palindromic T3 response element (TRE) at position -105/-87 in a manner that is prevented by T3 [27].

Regulatory relationships of TRNAE1

• Mutation of this TRE reduced the T3-enhanced androgenic activation of the PSA promoter [28].
• IGF-I and EGF stimulated the transcriptional activity dependent on the phorbol 12-myristate 13-acetate-responsive element (TRE) to the same extent, when measured by the chloramphenicol acetyl transferase activity of a transiently transfected multiple TRE construct [29].
• PTHrP activates CRE and TRE reporter constructs primarily through PKA-mediated signaling events [30].

Other interactions of TRNAE1

• The Ad5/SV40 integration site maps to identical chromosomal NotI fragments as RNU-1 and TRE [21].
• These results clearly indicate that cyclic strain inducibility of MCP-1 in ECs uses the interaction of AP-1 proteins with TRE sites via the elevation of intracellular ROS levels in strained ECs [16].
• In this study, we have characterized the functional properties of the TGGGTCA motif at -1/+6 of the hTSH beta gene that is similar to the consensus phorbol ester response element (TRE) or the consensus cyclic AMP response element (CRE) [31].
• We report an increased binding of AP-1 to TRE oligonucleotides in HMC cultured chronically (5 days) in high glucose environments (30 mM d-glucose) [25].
• (4) The differential dominant negative effect of mutant R316H (negative TRE > positive TRE) may explain, at least in part, the presentation of R316H as PRTH [10].

Analytical, diagnostic and therapeutic context of TRNAE1

• Studies using site-directed mutagenesis have shown that a basic region adjacent to the leucine zipper in Fos is crucial for the interaction of the Fos-Jun complex with the TRE, and probably represents a site of interaction with DNA [32].
• Electrophoretic mobility shift assays demonstrated an increase of nuclear proteins binding to TRE sequences from ECs subsequent to strain or H2O2 treatment [16].
• Sequence analysis revealed that this DH region was located in intron 1 and contained two TRE-like TGAT/ATCA elements, two 5'TTCA3' motifs and a 5'AGGAAG3' PEA3 motif [33].
• Tlag and TRE may confirm GE alteration, especially when solid T1/2 values are at the superior limit of normality, and may improve the performance of GE scintigraphy, rather than using liquid parameters [34].
• RT-PCR analyses of ORFs 4, 9, 21, 29 and 68 belonging to all three kinetic classes of genes and containing different combinations of AP1/TRE and ATF/CREB sites in their respective promoters were carried out [35].

References