A GCN‐like response in <i>Candida albicans</i>.

Pereira, Sarita A.; Livi, George P.

doi:10.1006/cbir.1995.1009

Cited by 12 publications

(11 citation statements)

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“…3 was simultaneously probed with a cDNA from the C. albicans CYP1 gene, encoding cytoplasmic cyclophilin, which recognizes an approximately 800 bp mRNA (Koser et al, 1990). The observed reduction in CYP1 mRNA in 3AT-treated cells is consistent with earlier findings, and is probably due to a drop in the overall rate of protein synthesis (Pereira & Livi, 1995). This result serves to accentuate the observed increase in ARO4-specific mRNA, and our estimates of the derepression ratio compare favourably with those of many starvation-induced genes in S. cerevisiae (data not shown ; Hinnebusch, 1990).…”

Section: Aro4 Mrna Levels Increase During Amino Acid Starvationsupporting

confidence: 91%

“…We previously cloned an ARO3 gene orthologue from the diploid pathogenic fungus C. albicans and found that it can complement an aro3 aro4 double mutation in S. cerevisiae, and that complementation is inhibited by excess phenylalanine (Pereira & Livi, 1993). Expression of C. albicans ARO3 mRNA is induced in response to amino acid starvation, consistent with the presence of two putative GCREs in the promoter sequence (Pereira & Livi, 1995). A homozygous aro3-deletion mutant strain was constructed and found to be prototrophic (Aro + ) on synthetic complete media lacking aromatic amino acids (Pereira & Livi, 1996), suggesting the existence of at least one additional isozyme.…”

Section: Introductionmentioning

confidence: 90%

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The ARO4 gene of Candida albicans encodes a tyrosine-sensitive DAHP synthase: evolution, functional conservation and phenotype of Aro3p-, Aro4p-deficient mutants The GenBank accession number for the sequence reported in this paper is U53216.

et al. 2002

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The enzyme 3-deoxy-D-arabinoheptulosonate-7-phosphate (DAHP) synthase catalyses the first step in aromatic amino acid biosynthesis in prokaryotes, plants and fungi. Cells of Saccharomyces cerevisiae contain two catalytically redundant DAHP synthases, encoded by the genes ARO3 and ARO4, whose activities are feedback-inhibited by phenylalanine and tyrosine, respectively. ARO3/4 gene transcription is controlled by GCN4. The authors previously cloned an ARO3 gene orthologue from Candida albicans and found that : (1) it can complement an aro3 aro4 double mutation in S. cerevisiae, an effect inhibited by excess phenylalanine, and (2) a homozygous aro3-deletion mutant of C. albicans is phenotypically Aro M , suggesting the existence of another isozyme(s). They now report the identification and functional characterization of the C. albicans orthologue of S. cerevisiae Aro4p. The two Aro4p enzymes share 68 % amino acid identity. Phylogenetic analysis places the fungal DAHP synthases in a cluster separate from prokaryotic orthologues and suggests that ARO3 and ARO4 arose from a single gene via a gene duplication event early in fungal evolution. C. albicans ARO4 mRNA is elevated upon amino acid starvation, consistent with the presence of three putative Gcn4p-responsive elements (GCREs) in the gene promoter sequence. C. albicans ARO4 complements an aro3 aro4 double mutation in S. cerevisiae, an effect inhibited by excess tyrosine. The authors engineered ∆aro3/∆aro3 ∆aro4/MET3p ::ARO4 cells of C. albicans (with one wild-type copy of ARO4 placed under control of the repressible MET3 promoter) and found that they fail to grow in the absence of aromatic amino acids when ARO4 expression is repressed, and that this growth defect can be partially rescued by aromatic amino acids and certain aromatic amino acid pathway intermediates. It is concluded that, like S. cerevisiae, C. albicans contains two DAHP synthases required for the first step in the aromatic amino acid biosynthetic pathway.

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Section: Aro4 Mrna Levels Increase During Amino Acid Starvationsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 90%

The ARO4 gene of Candida albicans encodes a tyrosine-sensitive DAHP synthase: evolution, functional conservation and phenotype of Aro3p-, Aro4p-deficient mutants The GenBank accession number for the sequence reported in this paper is U53216.

et al. 2002

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“…2), while a putative transcription termination signal was at 2943-2967 (based on their homology to S. cerevisiae consensus signals). No obvious S. cerevisiae GCN boxes (consensus sequence TGACTC) could be found in the 5'-upstream region, as has been observed for the C. albicans AR03 (Pereira & Livi, 1995) and A R G 4 (Hoyer et al, 1994) genes. In addition to the arg4 mutant strains 1006 and TMSU221, another complementation group designated argIOO has been described for strains A642, hOG318, hOG357, FC18-6 and WC-5-4 (Hoyer et al, 1994) located on the R chromosome.…”

Section: Sequence Analysis Of the C Albicans Arg56 Genesupporting

confidence: 54%

Cloning, analysis and one-step disruption of the ARG5,6 gene of Candida albicans

et al. 1997

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The ARG5,6 gene from the dimorphic fungus Candida albicans was cloned by functional complementation of the arginine auxotrophy present in strain EL2 (Arg') using a gene library constructed in the double autonomously replicating sequence vector pRMl. Sequence analysis revealed a putative 857 amino acid polypeptide (95 kDa) which showed high homology (63% protein identity) to the Saccharomyces cerevisiae ARG5,6 gene. Similarly to the S. cerevisiae gene, the C. albicans ARG5,6 gene is responsible for both the acetylglutamate kinase and acetylglutamyl-phosphate reductase activities, the second and third steps of arginine biosynthesis a t the mitochondria. The C. albicans ARG5,6 gene complemented the arg6 mutation present in 5. cerevisiae (strain Dl60-4D) on a yeast episomal plasmid using its own regulatory signals. A set of nonintegrative high-eff iciency plasmid vectors based on this gene marker was constructed and a null C. albicans arg5,6A strain was obtained using the common URA3-blaster strategy. In addition, we generated an arg5,6A null mutant in a single transformation event, thus improving the basic strategy for generating gene deletions in C* albicans.

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“…Phosphorylation of eIF2␣ can induce gene-specific translation important for coordinate expression of genes required to remedy cellular stress. While GCN4 homologues are also found in many other fungi, including Neurospora crassa (43), Aspergillus niger (78), and Candida albicans (55), there is no GCN4 homologue in S. pombe or in higher eukaryotic organisms. In mammalian cells, translational expression of another bZIP protein, ATF4, has been reported to be induced by GCN2 and PEK/Perk in response to amino acid limitation and ER stress, respectively (27).…”

Section: Fig 8 Loss Of Hri1mentioning

confidence: 99%

Phosphorylation of Eukaryotic Initiation Factor 2 by Heme-Regulated Inhibitor Kinase-Related Protein Kinases in Schizosaccharomyces pombe Is Important for Resistance to Environmental Stresses

Zhan

Vattem

Bauer

et al. 2002

Molecular and Cellular Biology

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Protein synthesis is regulated by the phosphorylation of the ␣ subunit of eukaryotic initiation factor 2 (eIF2␣) in response to different environmental stresses. One member of the eIF2␣ kinase family, hemeregulated inhibitor kinase (HRI), is activated under heme-deficient conditions and blocks protein synthesis, principally globin, in mammalian erythroid cells. We identified two HRI-related kinases from Schizosaccharomyces pombe which have full-length homology with mammalian HRI. The two HRI-related kinases, named Hri1p and Hri2p, exhibit autokinase and kinase activity specific for Ser-51 of eIF2␣, and both activities were inhibited in vitro by hemin, as previously described for mammalian HRI. Overexpression of Hri1p, Hri2p, or the human eIF2␣ kinase, double-stranded-RNA-dependent protein kinase (PKR), impeded growth of S. pombe due to elevated phosphorylation of eIF2␣. Cells from strains with deletions of the hri1 ؉ and hri2 ؉ genes, individually or in combination, exhibited a reduced growth rate when exposed to heat shock or to arsenic compounds. Measurements of in vivo phosphorylation of eIF2␣ suggest that Hri1p and Hri2p differentially phosphorylate eIF2␣ in response to these stress conditions. These results demonstrate that HRI-related enzymes are not unique to vertebrates and suggest that these eIF2␣ kinases are important participants in diverse stress response pathways in some lower eukaryotes.

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A GCN‐like response in Candida albicans.

Cited by 12 publications

References 11 publications

The ARO4 gene of Candida albicans encodes a tyrosine-sensitive DAHP synthase: evolution, functional conservation and phenotype of Aro3p-, Aro4p-deficient mutants The GenBank accession number for the sequence reported in this paper is U53216.

The ARO4 gene of Candida albicans encodes a tyrosine-sensitive DAHP synthase: evolution, functional conservation and phenotype of Aro3p-, Aro4p-deficient mutants The GenBank accession number for the sequence reported in this paper is U53216.

Cloning, analysis and one-step disruption of the ARG5,6 gene of Candida albicans

Phosphorylation of Eukaryotic Initiation Factor 2 by Heme-Regulated Inhibitor Kinase-Related Protein Kinases in Schizosaccharomyces pombe Is Important for Resistance to Environmental Stresses

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