Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.99.3 (PRE)
 1,923 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antirheumatic gold salt aurothiomalate (AuTM) has cellular actions that are consistent with modulation of gene expression. We have tested the hypothesis that an important mode of action of AuTM is inhibition of binding of certain transcription factors to regulatory elements in DNA. The chemistry of transcription factors containing the zinc finger motif makes them candidates for such an interaction with AuTM. In this regard, the interaction of a steroid hormone receptor, the progesterone receptor (PR), with its DNA response element (PRE) was chosen as a suitable model. Nuclear extracts of T-47D human breast cancer cells rich in PR were incubated with radiolabeled PRE, and binding was determined by gel retardation assay. Preincubation of nuclear extract with AuTM caused a concentration-dependent inhibition of binding of PR to PRE (IC50, approximately 3 microM). Other metal ions inhibited binding at higher concentrations, in a rank order correlating with their binding affinity for thiols. Thiomalic acid had no effect in the absence of gold in this system. To test the effect of AuTM on PR-mediated transcription, we transfected the progestin-inducible expression vector pMSG-CAT into T-47D cells. Transfected cells were incubated in the absence or presence of AuTM and treated with the synthetic progestin ORG2058, to induce chloramphenicol acetyl transferase (CAT) activity. With 10 and 100 microM AuTM, there was inhibition to 67 +/- 3% (p = 0.012) and 42 +/- 8% (p = 0.008) of CAT specific activity, respectively, compared with controls. These results demonstrate that AuTM can regulate gene expression and that inhibition of binding of a transcription factor to its response element is a likely mechanism. This provides a molecular model for further study of the antirheumatic action of gold salts.
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PMID:Inhibition of DNA binding and transcriptional activity of a nuclear receptor transcription factor by aurothiomalate and other metal ions. 194 34

We demonstrated previously that two molecules of steroid hormone receptor bound efficiently to a single hormone response element (GRE/PRE) of the tyrosine aminotransferase gene (Tsai et al., 1988). Here, we show that two tandemly linked GRE/PREs conferred progesterone inducibility synergistically to a heterologous TK-CAT fusion gene. Binding studies demonstrated that occupation of one GRE/PRE site by a progesterone receptor dimer increased the binding affinity of receptors for the second GRE/PRE site 100-fold. Thus, the observed synergistic induction of TK-CAT may result from cooperative binding of receptor dimers to the two GRE/PRE sites.
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PMID:Cooperative binding of steroid hormone receptors contributes to transcriptional synergism at target enhancer elements. 256 84

This study tested the hypothesis that live high, train low (LHTL) would increase submaximal exercise ventilation (V(E)) in normoxia, and the increase would be related to enhanced hypoxic ventilatory response (HVR). Thirty-three cyclists/triathletes were divided into three groups: 20 consecutive nights of hypoxia (LHTLc, n = 12), 20 nights of intermittent hypoxia (4x5-night 'blocks' of hypoxia interspersed by two nights of normoxia, LHTLi, n = 10), or control (CON, n = 11). LHTLc and LHTLi slept 8-10 h per night in normobaric hypoxia (2,650 m), and CON slept under ambient conditions (600 m). Resting, isocapnic HVR (DeltaV(E)/Deltablood oxygen saturation) was measured in normoxia before (PRE) and after 15 nights (N15) hypoxia. Submaximal cycle ergometry was conducted PRE and after 4, 10, and 19 nights of hypoxia (N4, N10, and N19 respectively). Mean submaximal exercise V(E) was increased (P < 0.05) from PRE to N4 in LHTLc [74.4 (5.1) vs 80.0 (8.4) l min(-1); mean (SD)] and in LHTLi [69.0 (7.5) vs 76.9 (7.3) l min(-1)] and remained elevated in both groups thereafter, with no changes observed in CON at any time. Prior to LHTL, submaximal V(E) was not correlated with HVR, but this relationship was significant at N4 (r = 0.49, P = 0.03) and N19 (r = 0.77, P < 0.0001). Additionally, the increases in submaximal V(E) and HVR from PRE to N15-N19 were correlated (r = 0.51, P = 0.02) for the pooled data of LHTLc and LHTLi. These results suggest that enhanced hypoxic chemosensitivity contributes to increased exercise V(E) in normoxia following LHTL.
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PMID:Hypoxic ventilatory response is correlated with increased submaximal exercise ventilation after live high, train low. 1560 29

JASMONATE ZIM-DOMAIN (JAZ) transcriptional repressors are key regulators of jasmonate (JA) signaling in plants. At the resting stage, the C-terminal Jas motifs of JAZ proteins bind the transcription factor MYC2 to repress JA signaling. Upon hormone elicitation, the Jas motif binds the hormone receptor CORONATINE INSENSITIVE1, which mediates proteasomal degradation of JAZs and thereby allowing the Mediator subunit MED25 to activate MYC2. Subsequently, plants desensitize JA signaling by feedback generation of dominant JAZ splice variants that repress MYC2. Here we report the mechanistic function of Arabidopsis (Arabidopsis thaliana) MED25 in regulating the alternative splicing of JAZ genes through recruiting the splicing factors PRE-mRNA-PROCESSING PROTEIN 39a (PRP39a) and PRP40a. We demonstrate that JA-induced generation of JAZ splice variants depends on MED25 and that MED25 recruits PRP39a and PRP40a to promote the full splicing of JAZ genes. Therefore, MED25 forms a module with PRP39a and PRP40a to prevent excessive desensitization of JA signaling mediated by JAZ splice variants.
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PMID:Mediator Subunit MED25 Couples Alternative Splicing of JAZ Genes with Fine-Tuning of Jasmonate Signaling. 3185 73