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Digitale Medien

A common drug-responsive element mediates the upregulation of the Candida albicans ABC transporters CDR1 and CDR2, two genes involved in antifungal drug resistance (2002)

Micheli, Michelle de ; Bille, Jacques ; Schueller, Christoph ; [weitere]

Oxford, UK : Blackwell Science Ltd.

Molecular microbiology 43 (2002), S. 0

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ISSN: 1365-2958

Quelle: Blackwell Publishing Journal Backfiles 1879-2005

Thema: Biologie , Medizin

Notizen: Upregulation of the ATP-binding cassette (ABC) transporter genes CDR1 and CDR2 (Candidadrug resistance 1 and 2) is a common mechanism observed in Candida albicans clinical isolates developing resistance to the class of azole antifungals. In this work, the regulatory elements of both genes were delimited using a reporter system in an azole-susceptible strain exposed to oestradiol, which allows transient induction of these genes. We found two regulatory elements in the CDR1 promoter: one responsible for basal expression (basal expression element; BEE) and the other required for oestradiol responsiveness (drug-responsive element I; DREI). In the CDR2 promoter, a single regulatory element responsible for oestradiol responsiveness (DREII) was detected. Both DREs shared a consensus of 21 bp with the sequence 5′-CGGA(A/T)ATCGGATATTTTTTTT-3′ having no equivalent to known eukaryotic regulatory sequence. Consistent with this finding, two other C. albicans genes identified by a search for the presence of DRE in the C. albicans genome sequence database were responsive to oestradiol. Finally, the regulatory elements found in CDR1 and CDR2 were also functional in an azole-resistant strain with constitutive high expression of both transporters. These results suggest that, although CDR1 and CDR2 upregulation can be obtained by transient drug-induced and constitutive upregulation, these two processes converge to the same regulatory elements and probably mobilize the same trans-acting factors.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1046/j.1365-2958.2002.02814.x

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2

Digitale Medien

The nuclear actin-related protein Act3p/Arp4p of Saccharomyces cerevisiae is involved in transcription regulation of stress genes (2003)

Görzer, Irene ; Schüller, Christoph ; Heidenreich, Erich ; [weitere]

Oxford, UK : Blackwell Publishing Ltd.

Molecular microbiology 50 (2003), S. 0

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ISSN: 1365-2958

Quelle: Blackwell Publishing Journal Backfiles 1879-2005

Thema: Biologie , Medizin

Notizen: A mutational analysis of the essential nuclear actin-related protein of Saccharomyces cerevisiae, Act3p/Arp4p, was performed. The five residues chosen for substitution were amino acids conserved between actin and Act3p/Arp4p, the tertiary structure of which most probably resembles that of actin. Two thermosensitive (ts) mutants, a single and a double point mutant, and one lethal double point mutant were obtained. Both ts mutants were formamide-sensitive which supports a structural relatedness of Act3p/Arp4p to actin; they were also hypersensitive against hydroxyurea and ultraviolet irradiation pointing to a possible role of Act3p/Arp4p in DNA replication and repair. Their ‘suppressor of Ty’ (SPT) phenotype, ob-served with another ts mutant of Act3p/Arp4p before, suggested involvement of Act3p/Arp4p in transcription regulation. Accordingly, genome-wide expression profiling revealed misregulated transcription in a ts mutant of a number of genes, among which increased expression of various stress-responsive genes (many of them requiring Msn2p/Msn4p for induction) was the most salient result. This provides an explanation for the mutant's enhanced resistance to severe thermal and oxidative stress. Thus, Act3p/Arp4p takes an important part in the repression of stress-induced genes under non-stress conditions.

Materialart: Digitale Medien

URL: http://dx.doi.org/10.1046/j.1365-2958.2003.03759.x

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