PMID- 11561289 OWN - NLM STAT- MEDLINE DCOM- 20011207 LR - 20171213 IS - 0749-503X (Print) IS - 0749-503X (Linking) VI - 18 IP - 13 DP - 2001 Sep 30 TI - Functional isolation of the Candida albicans FCR3 gene encoding a bZip transcription factor homologous to Saccharomyces cerevisiae Yap3p. PG - 1217-25 AB - We have isolated a C. albicans gene, named FCR3 (for fluconazole resistance 3), based upon its ability to suppress the FCZ hypersusceptibility of a Saccharomyces cerevisiae mutant strain (JY312) lacking the transcription factors Pdr1p and Pdr3p. The FCR3 ORF (1200 bp) encodes a 399 amino acid protein containing a basic leucine zipper (bZip) domain. Fcr3p displays the highest level of sequence homology with the S. cerevisiae Yap3p protein (34% identity, 45% similarity). We had previously shown that deletion of the PDR5 gene encoding a multidrug transporter completely abolished the ability of FCR3 to suppress the FCZ hypersusceptibility of JY312, suggesting that FCR3 confers FCZ resistance by activating PDR5 expression. We show here that the beta-galactosidase activity of a PDR5 promoter-lacZ construct in JY312 is increased two-fold upon FCR3 overexpression, demonstrating that FCR3 regulates PDR5 at the transcriptional level. We also show that FCR3 overexpression not only suppresses the hypersusceptibility of JY312 to 4-nitroquinoline-N-oxide (4-NQO) but also confers higher levels of resistance to this compound as compared to the wild-type KY320 strain. Since PDR5 is not involved in 4-NQO resistance, this result indicates that FCR3 can also activate the transcription of other genes that can confer 4-NQO resistance. Finally, Northern blot analysis indicates that FCR3 encodes a single 2.4 kb RNA transcript in C. albicans, suggesting that the FCR3 mRNA contains long 5' and/or 3' untranslated regions. The nucleotide sequence of the FCR3 gene has been deposited at GenBank under Accession No. AF342983. CI - Copyright 2001 John Wiley & Sons, Ltd. FAU - Yang, X AU - Yang X AD - Institut de Recherches Cliniques de Montreal, Montreal, Quebec, Canada H2W 1R7. FAU - Talibi, D AU - Talibi D FAU - Weber, S AU - Weber S FAU - Poisson, G AU - Poisson G FAU - Raymond, M AU - Raymond M LA - eng SI - GENBANK/AF342983 PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Yeast JT - Yeast (Chichester, England) JID - 8607637 RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Antifungal Agents) RN - 0 (Basic-Leucine Zipper Transcription Factors) RN - 0 (DNA-Binding Proteins) RN - 0 (G-Box Binding Factors) RN - 0 (Membrane Proteins) RN - 0 (PDR5 protein, S cerevisiae) RN - 0 (Saccharomyces cerevisiae Proteins) RN - 0 (Transcription Factors) RN - 8VZV102JFY (Fluconazole) RN - EC 3.4.23 (aspartic proteinase A) RN - EC 3.4.23.- (Aspartic Acid Endopeptidases) RN - EC 3.4.23.25 (YPS1 protein, S cerevisiae) SB - IM MH - ATP-Binding Cassette Transporters/genetics/metabolism MH - Amino Acid Sequence MH - Antifungal Agents/*pharmacology MH - Aspartic Acid Endopeptidases/*genetics MH - Basic-Leucine Zipper Transcription Factors MH - Candida albicans/drug effects/*genetics/metabolism MH - Cloning, Molecular MH - DNA-Binding Proteins/chemistry/*genetics/*metabolism MH - Drug Resistance, Fungal MH - Fluconazole/*pharmacology MH - G-Box Binding Factors MH - Membrane Proteins/genetics/metabolism MH - Molecular Sequence Data MH - Promoter Regions, Genetic MH - Saccharomyces cerevisiae/drug effects/genetics/metabolism MH - *Saccharomyces cerevisiae Proteins MH - Sequence Analysis, DNA MH - Transcription Factors/chemistry/*genetics/*metabolism MH - Transcriptional Activation EDAT- 2001/09/19 10:00 MHDA- 2002/01/05 10:01 CRDT- 2001/09/19 10:00 PHST- 2001/09/19 10:00 [pubmed] PHST- 2002/01/05 10:01 [medline] PHST- 2001/09/19 10:00 [entrez] AID - 10.1002/yea.770 [pii] AID - 10.1002/yea.770 [doi] PST - ppublish SO - Yeast. 2001 Sep 30;18(13):1217-25. doi: 10.1002/yea.770.