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Gene Review

YAP1  -  Yap1p

Saccharomyces cerevisiae S288c

Synonyms: AP-1-like transcription factor YAP1, PAR1, PDR4, Phenanthroline resistance protein PAR1, Pleiotropic drug resistance protein PDR4, ...
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Disease relevance of YAP1

  • The cadmium hypersensitivity of the delta yap1 mutant described here indicates that one major role of YAP1 in the yeast cell is to mediate resistance to this metal [1].
  • Thus, Yap1 is not directly involved in SRP1 induction by hypoxia, but is necessary to counteract the Ord1 effect [2].
  • Since ABC transporters are YAP1p transcription activator inducible, we included a yap1 mutant in our Sn2+ toxicity assay [3].

High impact information on YAP1


Chemical compound and disease context of YAP1


Biological context of YAP1

  • Changes in gene dosage of the YAP1 gene, encoding the yAP-1 transcriptional regulatory protein, cause profound alterations in cellular drug and metal resistance [10].
  • Strains lacking the YAP1 or GCN4 structural gene have very different phenotypes, which have been taken as evidence that these transcriptional regulatory proteins control separate batteries of target genes [11].
  • Taken collectively, our results demonstrate that FLR1 represents a new YAP1-controlled multidrug resistance molecular determinant in S. cerevisiae [12].
  • The role of the YAP1 and YAP2 genes in the regulation of the adaptive oxidative stress responses of Saccharomyces cerevisiae [13].
  • Whereas a Yap1p-responsive lacZ fusion gene was oxidant inducible in the presence of YAP1, the C. albicans Cap1p derivatives were not oxidant responsive in S. cerevisiae [14].

Anatomical context of YAP1

  • We have found that YAP1-mediated diazaborine resistance in the yeast Saccharomyces cerevisiae requires two efflux pumps, i.e. the major-facilitator-superfamily transporter Flr1p, which is located in the cytoplasmic membrane and the ATP-binding-cassette transporter Ycf1p which is present in the vacuolar membrane [15].
  • In this report, we identify naturally occurring nucleotide sequences that function as internal ribosome entry sites (IRESes) within the 5' leader sequences of Saccharomyces cerevisiae YAP1 and p150 mRNAs [16].

Associations of YAP1 with chemical compounds

  • Within the bZIP domain, ACR1 most strongly resembles the mammalian cyclic AMP-responsive transcriptional regulators CREB and CREM; it is less similar to GCN4 and YAP1, two previously described yeast bZIP transcriptional activators that recognize the related AP-1 sequence (consensus TGACTCA) [17].
  • YAP1 encodes a positive regulator with a leucine zipper motif that causes pleiotropic drug resistance when overproduced [18].
  • This allele of YAP1 carries a mutation that leads to a C620F exchange in the C-terminal cysteine-rich-domain region and is the first mutant of YAP1 that was isolated by a conventional genetic screen for drug resistance [15].
  • YAP1 was able to mediate both cadmium- and H2O2-induced transcriptional activation of an ARE-dependent promoter [19].
  • YAP1 confers resistance to the fatty acid synthase inhibitor cerulenin through the transporter Flr1p in Saccharomyces cerevisiae [20].

Physical interactions of YAP1

  • In an in vitro assay, we showed that Yap1p could directly bind to Pse1p and that this interaction was dissociated by Ran-GTP [21].
  • The RPN4 promoter contains an additional sequence that binds Yap1p, a bZIP-type transcription factor that plays an important role in the oxidative stress response and multidrug resistance [22].
  • DNA-affinity blots of proteins from YAP1 cells suggest the presence of additional TGACTCA-binding proteins other than GCN4 and yAP-1 [23].
  • Multiple Yap1p-binding sites mediate induction of the yeast major facilitator FLR1 gene in response to drugs, oxidants, and alkylating agents [8].
  • Indeed, Ybp1 forms a stress-induced complex with Yap1 in vivo and stimulates the nuclear accumulation of Yap1 in response to H2O2 but not in response to the thiol-oxidizing agent diamide [24].
  • In the present study, we show that Tsa1 can interact with Yap1 via disulfide linkages and induce the formation of intramolecular disulfide bonds in Yap1 in ybp1-1 cells [25].

Regulatory relationships of YAP1

  • Expression of ATR1 is enhanced in the presence of constitutively active alleles of YAP1 and GCN4 [11].
  • The expression of GSH1 in Saccharomyces cerevisiae has been known to be up-regulated by Yap1p, a critical transcription factor for the oxidative stress response in yeast [26].
  • The present study demonstrates that GSH2 expression is also regulated by Yap1p under oxidative stress-induced conditions [26].
  • In addition, TSA2 was activated in tsa1Delta cells in a Yap1p-dependent manner [27].
  • Transcription of YHB1 is not under the control of the transcriptional factor Yap1p [28].

Other interactions of YAP1


Analytical, diagnostic and therapeutic context of YAP1


  1. Yeast bZip proteins mediate pleiotropic drug and metal resistance. Wu, A., Wemmie, J.A., Edgington, N.P., Goebl, M., Guevara, J.L., Moye-Rowley, W.S. J. Biol. Chem. (1993) [Pubmed]
  2. A Rox1-independent hypoxic pathway in yeast. Antagonistic action of the repressor Ord1 and activator Yap1 for hypoxic expression of the SRP1/TIR1 gene. Bourdineaud, J.P., De Sampaïo, G., Lauquin, G.J. Mol. Microbiol. (2000) [Pubmed]
  3. Assessment of the stannous fluoride and phytic acid effect in the yeast Saccharomyces cerevislae. Lima-Filho, G.L., Pungartnik, C., Catanho, M.T., Bernardo-Filho, M. Cell. Mol. Biol. (Noisy-le-grand) (2002) [Pubmed]
  4. A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation. Delaunay, A., Pflieger, D., Barrault, M.B., Vinh, J., Toledano, M.B. Cell (2002) [Pubmed]
  5. par-1, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed. Guo, S., Kemphues, K.J. Cell (1995) [Pubmed]
  6. Exploring the metabolic and genetic control of gene expression on a genomic scale. DeRisi, J.L., Iyer, V.R., Brown, P.O. Science (1997) [Pubmed]
  7. Yap1p activates gene transcription in an oxidant-specific fashion. Coleman, S.T., Epping, E.A., Steggerda, S.M., Moye-Rowley, W.S. Mol. Cell. Biol. (1999) [Pubmed]
  8. 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]
  9. Yap1 overproduction restores arsenite resistance to the ABC transporter deficient mutant ycf1 by activating ACR3 expression. Bouganim, N., David, J., Wysocki, R., Ramotar, D. Biochem. Cell Biol. (2001) [Pubmed]
  10. GSH1, which encodes gamma-glutamylcysteine synthetase, is a target gene for yAP-1 transcriptional regulation. Wu, A.L., Moye-Rowley, W.S. Mol. Cell. Biol. (1994) [Pubmed]
  11. Saccharomyces cerevisiae basic region-leucine zipper protein regulatory networks converge at the ATR1 structural gene. Coleman, S.T., Tseng, E., Moye-Rowley, W.S. J. Biol. Chem. (1997) [Pubmed]
  12. 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]
  13. The role of the YAP1 and YAP2 genes in the regulation of the adaptive oxidative stress responses of Saccharomyces cerevisiae. Stephen, D.W., Rivers, S.L., Jamieson, D.J. Mol. Microbiol. (1995) [Pubmed]
  14. Analysis of the oxidative stress regulation of the Candida albicans transcription factor, Cap1p. Zhang, X., De Micheli, M., Coleman, S.T., Sanglard, D., Moye-Rowley, W.S. Mol. Microbiol. (2000) [Pubmed]
  15. Diazaborine resistance in yeast involves the efflux pumps Ycf1p and Flr1p and is enhanced by a gain-of-function allele of gene YAP1. Jungwirth, H., Wendler, F., Platzer, B., Bergler, H., Högenauer, G. Eur. J. Biochem. (2000) [Pubmed]
  16. Transcript leader regions of two Saccharomyces cerevisiae mRNAs contain internal ribosome entry sites that function in living cells. Zhou, W., Edelman, G.M., Mauro, V.P. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  17. ACR1, a yeast ATF/CREB repressor. Vincent, A.C., Struhl, K. Mol. Cell. Biol. (1992) [Pubmed]
  18. Mutations in the yeast PDR3, PDR4, PDR7 and PDR9 pleiotropic (multiple) drug resistance loci affect the transcript level of an ATP binding cassette transporter encoding gene, PDR5. Dexter, D., Moye-Rowley, W.S., Wu, A.L., Golin, J. Genetics (1994) [Pubmed]
  19. Stress-induced transcriptional activation mediated by YAP1 and YAP2 genes that encode the Jun family of transcriptional activators in Saccharomyces cerevisiae. Hirata, D., Yano, K., Miyakawa, T. Mol. Gen. Genet. (1994) [Pubmed]
  20. 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]
  21. Nuclear import of the yeast AP-1-like transcription factor Yap1p is mediated by transport receptor Pse1p, and this import step is not affected by oxidative stress. Isoyama, T., Murayama, A., Nomoto, A., Kuge, S. J. Biol. Chem. (2001) [Pubmed]
  22. Control of 26S proteasome expression by transcription factors regulating multidrug resistance in Saccharomyces cerevisiae. Owsianik, G., Balzi l, L., Ghislain, M. Mol. Microbiol. (2002) [Pubmed]
  23. Yeast YAP1 encodes a novel form of the jun family of transcriptional activator proteins. Moye-Rowley, W.S., Harshman, K.D., Parker, C.S. Genes Dev. (1989) [Pubmed]
  24. Ybp1 is required for the hydrogen peroxide-induced oxidation of the Yap1 transcription factor. Veal, E.A., Ross, S.J., Malakasi, P., Peacock, E., Morgan, B.A. J. Biol. Chem. (2003) [Pubmed]
  25. A major peroxiredoxin-induced activation of Yap1 transcription factor is mediated by reduction-sensitive disulfide bonds and reveals a low level of transcriptional activation. Tachibana, T., Okazaki, S., Murayama, A., Naganuma, A., Nomoto, A., Kuge, S. J. Biol. Chem. (2009) [Pubmed]
  26. The Yap1p-dependent induction of glutathione synthesis in heat shock response of Saccharomyces cerevisiae. Sugiyama, K., Izawa, S., Inoue, Y. J. Biol. Chem. (2000) [Pubmed]
  27. Cooperation of yeast peroxiredoxins Tsa1p and Tsa2p in the cellular defense against oxidative and nitrosative stress. Wong, C.M., Zhou, Y., Ng, R.W., Kung Hf, H.F., Jin, D.Y. J. Biol. Chem. (2002) [Pubmed]
  28. Flavohemoglobin expression and function in Saccharomyces cerevisiae. No relationship with respiration and complex response to oxidative stress. Buisson, N., Labbe-Bois, R. J. Biol. Chem. (1998) [Pubmed]
  29. Genetic analysis of glutathione peroxidase in oxidative stress response of Saccharomyces cerevisiae. Inoue, Y., Matsuda, T., Sugiyama, K., Izawa, S., Kimura, A. J. Biol. Chem. (1999) [Pubmed]
  30. Hydrogen peroxide-induced carbonylation of key metabolic enzymes in Saccharomyces cerevisiae: the involvement of the oxidative stress response regulators Yap1 and Skn7. Costa, V.M., Amorim, M.A., Quintanilha, A., Moradas-Ferreira, P. Free Radic. Biol. Med. (2002) [Pubmed]
  31. Yap1 and Skn7 control two specialized oxidative stress response regulons in yeast. Lee, J., Godon, C., Lagniel, G., Spector, D., Garin, J., Labarre, J., Toledano, M.B. J. Biol. Chem. (1999) [Pubmed]
  32. Mutational analysis of Yap1 protein, an AP-1-like transcriptional activator of Saccharomyces cerevisiae. Takeuchi, T., Miyahara, K., Hirata, D., Miyakawa, T. FEBS Lett. (1997) [Pubmed]
  33. Discrimination between paralogs using microarray analysis: application to the Yap1p and Yap2p transcriptional networks. Cohen, B.A., Pilpel, Y., Mitra, R.D., Church, G.M. Mol. Biol. Cell (2002) [Pubmed]
  34. Role of thioredoxin reductase in the Yap1p-dependent response to oxidative stress in Saccharomyces cerevisiae. Carmel-Harel, O., Stearman, R., Gasch, A.P., Botstein, D., Brown, P.O., Storz, G. Mol. Microbiol. (2001) [Pubmed]
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