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

The facB gene of Aspergillus nidulans encodes a DNA binding transcriptional activator required for growth on acetate as a sole carbon source. FacB contains N-terminal GAL4-like Zn(II)2Cys6 (or C6 zinc) binuclear cluster DNA binding and leucine zipper-like heptad repeat motifs and central and C-terminal acidic alpha-helical regions. facB recessive loss of function mutants are deficient in acetate induction of acetyl-CoA synthase, isocitrate lyase, malate synthase, acetamidase, and NADP-isocitrate dehydrogenase. Characterization of lesions in facB mutant alleles has localized important functional regions of the FacB protein. Two extreme mutants are shown to lack the C-terminal region of the protein. Two temperature sensitive mutants contain amino acid substitutions in the DNA binding domain and are shown to affect acetate induction of amdS-lacZ expression and confer temperature sensitive in vitro DNA binding. Two temperature sensitive facB mutations result in thermolability of acetyl-CoA synthase, isocitrate lyase, and malate synthase but not acetamidase or NADP-isocitrate dehydrogenase in crude extracts. This suggests that FacB may have a structural role in acetate metabolism in addition to its regulatory function.
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PMID:Molecular characterization of mutants of the acetate regulatory gene facB of Aspergillus nidulans. 936 56

The facB gene is required for acetate induction of acetamidase (amdS) and the acetate utilization enzymes acetyl-CoA synthase (facA), isocitrate lyase (acuD) and malate synthase (acuE) in Aspergillus nidulans. The facB gene encodes a transcriptional activator with a GAL4-type Zn(II)2Cys6 zinc binuclear cluster DNA-binding domain which is shown to be required for DNA binding. In vitro DNA-binding sites for FacB in the 5' regions of the amdS, facA, acuD and acuE genes have been identified. Mutations in amdS FacB DNA-binding sites affected expression of an amdS-lacZ reporter in vivo and altered the affinity of in vitro DNA binding. This study shows that the FacB Zn(II)2Cys6 cluster binds to dissimilar sites which show similarity in form but not sequence with DNA-binding sites of other Zn(II)2Cys6 proteins. Sequences with homology to FacB sites are found in the 5' regions of genes regulated by the closely related yeast Zn(II)2Cys6 protein CAT8.
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PMID:FacB, the Aspergillus nidulans activator of acetate utilization genes, binds dissimilar DNA sequences. 952 26

The yeast Kluyveromyces lactis is can utilise a wide range of non-fermentable carbon compounds as sole sources of carbon and energy, and differs from Saccharomyces cerevisiae in being able to carry out oxidative and fermentative metabolism simultaneously. In S. cerevisiae, growth on all non-fermentable carbon sources requires Cat8p, a transcriptional activator that controls the expression of gluconeogenic and glyoxylate cycle genes via CSREs (Carbon Source Responsive Elements). The down-regulation of Cat8p by fermentable carbon sources is the primary factor responsible for the tight repression of gluconeogenesis by glucose in S. cerevisiae. To analyse the regulation of gluconeogenesis in K. lactis, we have cloned and characterised the K. lactis homologue of CAT8 (KlCAT8). The gene was isolated by multicopy suppression of a fog2/klsnf1 mutation, indicating a similar epistatic relationship between KlSNF1 and KlCAT8 as in the case of the S. cerevisiae homologues. KlCAT8 encodes a protein of 1445 amino acids that is 40% identical to ScCat8p. The most highly conserved block is the putative Zn(II)2Cys6 DNA-binding domain, but additional conserved regions shared with members of the zinc-cluster family from Aspergillus define a subfamily of Cat8p-related proteins. KlCAT8 complements the growth defect of a Sccat8 mutant on non-fermentable carbon sources. In K. lactis, deletion of KlCAT8 severely impairs growth on ethanol, acetate and lactate, but not on glycerol. Derepression of enzymes of the glyoxylate cycle--malate synthase and particularly isocitrate lyase--was impaired in a Klcat8 mutant, whereas Northern analysis revealed that derepression of KlFBP1 and KlPCK1 does not require KlCat8p. Taken together, our results indicate that in K. lactis gluconeogenesis is not co-regulated with the glyoxylate cycle, and only the latter is controlled by KlCat8p.
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PMID:Differences in regulation of yeast gluconeogenesis revealed by Cat8p-independent activation of PCK1 and FBP1 genes in Kluyveromyces lactis. 1101 49

In Corynebacterium glutamicum, the acetate-activating enzymes phosphotransacetylase and acetate kinase and the glyoxylate cycle enzymes isocitrate lyase and malate synthase are coordinately up-regulated in the presence of acetate in the growth medium. This regulation is due to transcriptional control of the respective pta-ack operon and the aceA and aceB genes, brought about at least partly by the action of the negative transcriptional regulator RamB. Using cell extracts of C. glutamicum and employing DNA affinity chromatography, mass spectrometry, and peptide mass fingerprinting, we identified a LuxR-type transcriptional regulator, designated RamA, which binds to the pta-ack and aceA/aceB promoter regions. Inactivation of the ramA gene in the genome of C. glutamicum resulted in mutant RG2. This mutant was unable to grow on acetate as the sole carbon and energy source and, in comparison to the wild type of C. glutamicum, showed very low specific activities of phosphotransacetylase, acetate kinase, isocitrate lyase, and malate synthase, irrespective of the presence of acetate in the medium. Comparative transcriptional cat fusion experiments revealed that this deregulation takes place at the level of transcription. By electrophoretic mobility shift analysis, purified His-tagged RamA protein was shown to bind specifically to the pta-ack and the aceA/aceB promoter regions, and deletion and mutation studies revealed in both regions two binding motifs each consisting of tandem A/C/TG4-6T/C or AC4-5A/G/T stretches separated by four or five arbitrary nucleotides. Our data indicate that RamA represents a novel LuxR-type transcriptional activator of genes involved in acetate metabolism of C. glutamicum.
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PMID:Identification of RamA, a novel LuxR-type transcriptional regulator of genes involved in acetate metabolism of Corynebacterium glutamicum. 1654 43