Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heavy metal-induced transcriptional activation of the genes coding for metallothionein (MT) is mediated by a cis-acting DNA element, the metal-responsive element (MRE). MRE-binding transcription factor-1 (MTF-1) is a highly conserved heavy metal-induced transcriptional activator. MTF-1 also activates transcription in response to oxidative stress and regulates the expression of several cytoprotective factor genes, including MT, gamma-glutamylcysteine synthetase, and Cu/Zn-superoxide dismutase. It is thus thought that MTF-1 plays a role in cellular stress response. The physiological role of MTF-1 remains unclear because of the lack of MTF-1-specific activators and/or inhibitors. To obtain an MTF-1-specific inhibitor, we constructed an MTFDeltaC (amino acids 1-317), a C-terminal deletion mutant of MTF-1. MTFDeltaC could bind MRE and competed with MTF-1 for MTF-MRE complex formation. Transient expression of MTFDeltaC in HepG2 cells reduced MRE-driven gene expression, demonstrating that MTFDeltaC is dominant to MTF-1. HepG2 cells stably expressing MTFDeltaC showed increased susceptibility to the cytotoxic effects of tert-butyl hydroperoxide (tBH). Furthermore, we constructed Ad5MTFDeltaC, a recombinant adenovirus that expresses MTFDeltaC. Infection with the virus induced MTFDeltaC expression and increased susceptibility to the cytotoxic effects of tBH. These results indicate that MTF-1 participates in controlling the cellular redox state.
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PMID:C-terminal deletion mutant of MRE-binding transcription factor-1 inhibits MRE-driven gene expression. 1537 1

katA and ahpC, encoding monofunctional catalase and alkyl hydroperoxide reductase, respectively, play important protective roles against peroxide toxicity in Xanthomonas campestris pv. phaseoli (Xp). The expression of both katA and ahpC is controlled by the global peroxide sensor and transcriptional activator, OxyR. In Xp, these two genes have compensatory expression patterns. Inactivation of katA leads to an increase in the level of AhpC and a concomitant increase in resistance to tert-butyl hydroperoxide (tBOOH). High-level expression of katA from an expression vector in Xp also lowered the level of ahpC expression. The compensatory regulation of katA and ahpC was mediated by OxyR, since the compensatory response was not observed in an oxyR mutant background. ahpC and katA play important but unequal roles in protecting Xp from H(2)O(2) toxicity. These observations, taken together with a previous observation that an ahpC mutant expresses high levels of KatA and is hyper-resistant to H(2)O(2), suggest the possibility that inactivation of either gene leads to accumulation of intracellular H(2)O(2). This in turn oxidizes reduced OxyR and converts the regulator to the oxidized form that then activates expression of genes in the OxyR regulon.
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PMID:OxyR mediated compensatory expression between ahpC and katA and the significance of ahpC in protection from hydrogen peroxide in Xanthomonas campestris. 1599 9