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Gene Review

FLR1  -  Flr1p

Saccharomyces cerevisiae S288c

Synonyms: Fluconazole resistance protein 1, YBR008C, YBR0120
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Disease relevance of FLR1


High impact information on FLR1

  • Some genes, such as YOR1, SNQ2, and FLR1, are clearly directly controlled by both classes of transcription factor, suggesting an important role for the corresponding membrane proteins [6].
  • Expression of FLR1 transporter requires phospholipase C and is repressed by Mediator [7].
  • FLR1 encodes a plasma membrane transporter that mediates resistance to benomyl [7].
  • Several other mutations in the Mediator complex also result in significant derepression of FLR1 and greatly increased resistance to benomyl [7].
  • Multiple Yap1p-binding sites mediate induction of the yeast major facilitator FLR1 gene in response to drugs, oxidants, and alkylating agents [1].

Chemical compound and disease context of FLR1


Biological context of FLR1

  • AP1-mediated multidrug resistance in Saccharomyces cerevisiae requires FLR1 encoding a transporter of the major facilitator superfamily [9].
  • Our results show that (i) each of the three YREs is functional and important for the optimal transactivation of FLR1 by Yap1p and that (ii) the three YREs are not functionally equivalent, mutation of YRE3 being the most deleterious, followed by YRE2 and YRE1 [1].
  • The FLR1 promoter contains three potential Yap1p response elements (YREs) at positions -148 (YRE1), -167 (YRE2), and -364 (YRE3) [1].
  • Our conclusions were based on the higher susceptibility to these compounds of flr1Delta compared with wild-type and on the increased resistance of both flr1Delta and wild-type strains upon increased expression of FLR1 gene from a centromeric plasmid clone [10].
  • The present study also provides, for the first time, evidence that the adaptation of yeast cells to growth in the presence of benomyl involves the dramatic activation of FLR1 gene expression during benomyl-induced latency (up to 400-fold) [10].

Anatomical context of FLR1


Associations of FLR1 with chemical compounds


Regulatory relationships of FLR1

  • Results obtained using a FLR1-lacZ fusion in a plasmid indicate that the activation of FLR1 expression in benomyl-stressed cells is under the control of the transcriptional regulator Pdr3p [10].

Other interactions of FLR1


Analytical, diagnostic and therapeutic context of FLR1


  1. Multiple Yap1p-binding sites mediate induction of the yeast major facilitator FLR1 gene in response to drugs, oxidants, and alkylating agents. Nguyên, D.T., Alarco, A.M., Raymond, M. J. Biol. Chem. (2001) [Pubmed]
  2. Correlation of in vitro fluconazole resistance of Candida isolates in relation to therapy and symptoms of individuals seropositive for human immunodeficiency virus type 1. Cameron, M.L., Schell, W.A., Bruch, S., Bartlett, J.A., Waskin, H.A., Perfect, J.R. Antimicrob. Agents Chemother. (1993) [Pubmed]
  3. Epidemiology of oral candidiasis in HIV-infected patients: colonization, infection, treatment, and emergence of fluconazole resistance. Sangeorzan, J.A., Bradley, S.F., He, X., Zarins, L.T., Ridenour, G.L., Tiballi, R.N., Kauffman, C.A. Am. J. Med. (1994) [Pubmed]
  4. Detection and significance of fluconazole resistance in oropharyngeal candidiasis in human immunodeficiency virus-infected patients. Revankar, S.G., Kirkpatrick, W.R., McAtee, R.K., Dib, O.P., Fothergill, A.W., Redding, S.W., Rinaldi, M.G., Patterson, T.F. J. Infect. Dis. (1996) [Pubmed]
  5. Molecular characterization of fluconazole resistance in a case of Candida albicans ocular infection. Pancholi, P., Park, S., Perlin, D., Kubin, C., Della-Latta, P. J. Clin. Microbiol. (2004) [Pubmed]
  6. New insights into the pleiotropic drug resistance network from genome-wide characterization of the YRR1 transcription factor regulation system. Le Crom, S., Devaux, F., Marc, P., Zhang, X., Moye-Rowley, W.S., Jacq, C. Mol. Cell. Biol. (2002) [Pubmed]
  7. Expression of FLR1 transporter requires phospholipase C and is repressed by Mediator. Romero, C., Desai, P., DeLillo, N., Vancura, A. J. Biol. Chem. (2006) [Pubmed]
  8. Isolation of a putative Candida albicans transcriptional regulator involved in pleiotropic drug resistance by functional complementation of a pdr1 pdr3 mutation in Saccharomyces cerevisiae. Talibi, D., Raymond, M. J. Bacteriol. (1999) [Pubmed]
  9. AP1-mediated multidrug resistance in Saccharomyces cerevisiae requires FLR1 encoding a transporter of the major facilitator superfamily. Alarco, A.M., Balan, I., Talibi, D., Mainville, N., Raymond, M. J. Biol. Chem. (1997) [Pubmed]
  10. FLR1 gene (ORF YBR008c) is required for benomyl and methotrexate resistance in Saccharomyces cerevisiae and its benomyl-induced expression is dependent on pdr3 transcriptional regulator. Brôco, N., Tenreiro, S., Viegas, C.A., Sá-Correia, I. Yeast (1999) [Pubmed]
  11. Transcriptional activation of FLR1 gene during Saccharomyces cerevisiae adaptation to growth with benomyl: role of Yap1p and Pdr3p. Tenreiro, S., Fernandes, A.R., Sá-Correia, I. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  12. Oropharyngeal yeast flora and fluconazole resistance in HIV-infected patients receiving long-term continuous versus intermittent fluconazole therapy. Heald, A.E., Cox, G.M., Schell, W.A., Bartlett, J.A., Perfect, J.R. AIDS (1996) [Pubmed]
  13. YAP1 confers resistance to the fatty acid synthase inhibitor cerulenin through the transporter Flr1p in Saccharomyces cerevisiae. Oskouian, B., Saba, J.D. Mol. Gen. Genet. (1999) [Pubmed]
  14. The bZip transcription factor Cgap1p is involved in multidrug resistance and required for activation of multidrug transporter gene CgFLR1 in Candida glabrata. Chen, K.H., Miyazaki, T., Tsai, H.F., Bennett, J.E. Gene (2007) [Pubmed]
  15. The mutation T315A in Candida albicans sterol 14alpha-demethylase causes reduced enzyme activity and fluconazole resistance through reduced affinity. Lamb, D.C., Kelly, D.E., Schunck, W.H., Shyadehi, A.Z., Akhtar, M., Lowe, D.J., Baldwin, B.C., Kelly, S.L. J. Biol. Chem. (1997) [Pubmed]
  16. Regulation of azole drug susceptibility by Candida albicans protein kinase CK2. Bruno, V.M., Mitchell, A.P. Mol. Microbiol. (2005) [Pubmed]
  17. Capisterones A and B, which Enhance Fluconazole Activity in Saccharomyces cerevisiae, from the Marine Green Alga Penicillus capitatus. Li, X.C., Jacob, M.R., Ding, Y., Agarwal, A.K., Smillie, T.J., Khan, S.I., Nagle, D.G., Ferreira, D., Clark, A.M. J. Nat. Prod. (2006) [Pubmed]
  18. Overexpression of Erg11p by the regulatable GAL1 promoter confers fluconazole resistance in Saccharomyces cerevisiae. Kontoyiannis, D.P., Sagar, N., Hirschi, K.D. Antimicrob. Agents Chemother. (1999) [Pubmed]
  19. Reversible fluconazole resistance in Candida albicans: a potential in vitro model. Calvet, H.M., Yeaman, M.R., Filler, S.G. Antimicrob. Agents Chemother. (1997) [Pubmed]
  20. Molecular epidemiology of Candida albicans strains isolated from the oropharynx of HIV-positive patients at successive clinic visits. Lasker, B.A., Elie, C.M., Lott, T.J., Espinel-Ingroff, A., Gallagher, L., Kuykendall, R.J., Kellum, M.E., Pruitt, W.R., Warnock, D.W., Rimland, D., McNeil, M.M., Reiss, E. Med. Mycol. (2001) [Pubmed]
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