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)

Although oxidative stress is involved in many human diseases, little is known of its molecular basis in eukaryotes. In a genetic approach, S. cerevisiae was used to identify elements involved in oxidative stress. By using hydrogen peroxide as an agent for oxidative stress, 34 mutants were identified. All mutants were recessive and fell into 16 complementation groups (pos1 to pos16 for peroxide sensitivity). They corresponded to single mutations as shown by a 2:2 segregation pattern. Enzymes reportedly involved in oxidative stress, such as glucose-6-phosphate dehydrogenase, glutathione reductase, superoxide dismutase, as well as glutathione concentrations, were investigated in wild-type and mutant-cells. One complementation group lacked glucose-6-phosphate dehydrogenase and was shown to be allelic to the glucose-6-phosphate dehydrogenase structural gene ZWF1/MET19. In other mutants all enzymes supposedly involved in oxidative-stress resistance were still present. However, several mutants showed strongly elevated levels of glutathione reductase, gluconate-6-phosphate dehydrogenase and glucose-6-phosphate dehydrogenase. One complementation group, pos9, was highly sensitive to oxidative stress and revealed the same growth phenotype as the previously described yap1/par1 mutant coding for the yeast homologue of mammalian transcriptional activator protein, c-Jun, of the proto-oncogenic AP-1 complex. However, unlike par1 mutants, which showed diminished activities of oxidative-stress enzymes and glutathion level, the pos9 mutants did not reveal any such changes. In contrast to other recombinants between pos mutations and par1, the sensitivity did not further increase in par1 pos9 recombinants, which may indicate that both mutations belong to the same regulating circuit.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mutants of Saccharomyces cerevisiae sensitive to oxidative and osmotic stress. 758 28

Crc (catabolite repression control) protein of Pseudomonas aeruginosa has shown to be involved in carbon regulation of several pathways. In this study, the role of Crc in catabolite repression control has been studied in Pseudomonas putida. The bkd operons of P. putida and P. aeruginosa encode the inducible multienzyme complex branched-chain keto acid dehydrogenase, which is regulated in both species by catabolite repression. We report here that this effect is mediated in both species by Crc. A 13-kb cloned DNA fragment containing the P. putida crc gene region was sequenced. Crc regulates the expression of branched-chain keto acid dehydrogenase, glucose-6-phosphate dehydrogenase, and amidase in both species but not urocanase, although the carbon sources responsible for catabolite repression in the two species differ. Transposon mutants affected in their expression of BkdR, the transcriptional activator of the bkd operon, were isolated and identified as crc and vacB (rnr) mutants. These mutants suggested that catabolite repression in pseudomonads might, in part, involve control of BkdR levels.
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PMID:Crc is involved in catabolite repression control of the bkd operons of Pseudomonas putida and Pseudomonas aeruginosa. 1064 42

Deletions were made in Streptomyces lividans in either of two genes (zwf1 and zwf2) encoding isozymes of glucose-6-phosphate dehydrogenase, the first enzyme in the oxidative pentose phosphate pathway (PPP). Each mutation reduced the level of Zwf activity to approximately one-half that observed in the wild-type strain. When the mutants were transformed with multicopy plasmids carrying the pathway-specific transcriptional activator genes for either the actinorhodin (ACT) or undecylprodigiosin (RED) biosynthetic pathway, they produced higher levels of antibiotic than the corresponding wild-type control strains. The presumed lower flux of carbon through the PPP in each of the Deltazwf mutants may allow more efficient glucose utilization via glycolysis, resulting in higher levels of antibiotic production. This appears to occur without lowering the concentration of NADPH (the major biochemical product of the oxidative PPP activity) to a level that would limit antibiotic biosynthesis. Consistent with this hypothesis, deletion of the gene (devB) encoding the enzyme that catalyzes the next step in the oxidative PPP (6-phosphogluconolactonase) also resulted in increased antibiotic production. However, deletion of both zwf genes from the devB mutant resulted in reduced levels of ACT and RED production, suggesting that some of the NADPH made by the PPP is utilized, directly or indirectly, for antibiotic biosynthesis. Although applied here to the model antibiotics ACT and RED, such mutations may prove to be useful for improving the yield of commercially important secondary metabolites.
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PMID:Engineering of primary carbon metabolism for improved antibiotic production in Streptomyces lividans. 1232 14

Global transcription studies have identified a large number of redox-responsive genes, although the biological relevance of this regulation has not been experimentally tested. In particular, several genes coding for enzymes involved in glucose metabolism have been identified as redox-responsive in Escherichia coli. However, only zwf, which codes for glucose-6-phosphate dehydrogenase, has been shown experimentally to affect the cellular resistance to oxidative stress. We addressed the question of whether ptsG, coding for the membrane component of the glucose-specific transporter system, and pgi, coding for phosphoglucose isomerase, two additional genes identified in whole-genome functional screens, are indeed relevant in antioxidant defense. PTS assays showed that glucose transport was induced under oxidative stress elicited by the superoxide-producing agent paraquat (PQ). This induction of glucose transport under oxidative stress was dependent on the soxRS genes, coding for a sensor- transcriptional activator system, and ptsG. The binding of purified SoxS to the ptsG promoter region was shown by gel mobility-shift assay, and the activation of the ptsG promoter P1 was demonstrated by primer extension assays. Finally, a ptsG mutant strain was hypersensitive to PQ when grown in rich medium plus glucose, but not in rich medium without glucose. The pgi gene showed the same pattern of regulation by oxidative stress under the control of the SoxRS system, and a strain carrying a pgi deletion was hypersensitive to PQ.
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PMID:Activation of glucose transport under oxidative stress in Escherichia coli. 1836 88