• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Dec 1997; 17(12): 6982–6993.
PMCID: PMC232555

Yap, a novel family of eight bZIP proteins in Saccharomyces cerevisiae with distinct biological functions.

Abstract

Saccharomyces cerevisiae contains eight members of a novel and fungus-specific family of bZIP proteins that is defined by four atypical residues on the DNA-binding surface. Two of these proteins, Yap1 and Yap2, are transcriptional activators involved in pleiotropic drug resistance. Although initially described as AP-1 factors, at least four Yap proteins bind most efficiently to TTACTAA, a sequence that differs at position +/-2 from the optimal AP-1 site (TGACTCA); further, a Yap-like derivative of the AP-1 factor Gcn4 (A239Q S242F) binds efficiently to the Yap recognition sequence. Molecular modeling suggests that the Yap-specific residues make novel contacts and cause physical constraints at the +/-2 position that may account for the distinct DNA-binding specificities of Yap and AP-1 proteins. To various extents, Yap1, Yap2, Yap3, and Yap5 activate transcription from a promoter containing a Yap recognition site. Yap-dependent transcription is abolished in strains containing high levels of protein kinase A; in contrast, Gcn4 transcriptional activity is stimulated by protein kinase A. Interestingly, Yap1 transcriptional activity is stimulated by hydrogen peroxide, whereas Yap2 activity is stimulated by aminotriazole and cadmium. In addition, unlike other yap mutations tested, yap4 (cin5) mutations affect chromosome stability, and they suppress the cold-sensitive phenotype of yap1 mutant strains. Thus, members of the Yap family carry out overlapping but distinct biological functions.

Full Text

The Full Text of this article is available as a PDF (1.9M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Alarco AM, Balan I, Talibi D, Mainville N, Raymond M. AP1-mediated multidrug resistance in Saccharomyces cerevisiae requires FLR1 encoding a transporter of the major facilitator superfamily. J Biol Chem. 1997 Aug 1;272(31):19304–19313. [PubMed]
  • Angel P, Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129–157. [PubMed]
  • Bohmann D, Bos TJ, Admon A, Nishimura T, Vogt PK, Tjian R. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science. 1987 Dec 4;238(4832):1386–1392. [PubMed]
  • Boorstein WR, Craig EA. Regulation of a yeast HSP70 gene by a cAMP responsive transcriptional control element. EMBO J. 1990 Aug;9(8):2543–2553. [PMC free article] [PubMed]
  • Bossier P, Fernandes L, Rocha D, Rodrigues-Pousada C. Overexpression of YAP2, coding for a new yAP protein, and YAP1 in Saccharomyces cerevisiae alleviates growth inhibition caused by 1,10-phenanthroline. J Biol Chem. 1993 Nov 5;268(31):23640–23645. [PubMed]
  • Broach JR. RAS genes in Saccharomyces cerevisiae: signal transduction in search of a pathway. Trends Genet. 1991 Jan;7(1):28–33. [PubMed]
  • Chatterjee S, Struhl K. Connecting a promoter-bound protein to TBP bypasses the need for a transcriptional activation domain. Nature. 1995 Apr 27;374(6525):820–822. [PubMed]
  • Distel RJ, Ro HS, Rosen BS, Groves DL, Spiegelman BM. Nucleoprotein complexes that regulate gene expression in adipocyte differentiation: direct participation of c-fos. Cell. 1987 Jun 19;49(6):835–844. [PubMed]
  • Dombek KM, Young ET. Cyclic AMP-dependent protein kinase inhibits ADH2 expression in part by decreasing expression of the transcription factor gene ADR1. Mol Cell Biol. 1997 Mar;17(3):1450–1458. [PMC free article] [PubMed]
  • Ellenberger TE, Brandl CJ, Struhl K, Harrison SC. The GCN4 basic region leucine zipper binds DNA as a dimer of uninterrupted alpha helices: crystal structure of the protein-DNA complex. Cell. 1992 Dec 24;71(7):1223–1237. [PubMed]
  • Engelberg D, Klein C, Martinetto H, Struhl K, Karin M. The UV response involving the Ras signaling pathway and AP-1 transcription factors is conserved between yeast and mammals. Cell. 1994 May 6;77(3):381–390. [PubMed]
  • Gietz RD, Sugino A. New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites. Gene. 1988 Dec 30;74(2):527–534. [PubMed]
  • Glover JN, Harrison SC. Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA. Nature. 1995 Jan 19;373(6511):257–261. [PubMed]
  • Gounalaki N, Thireos G. Yap1p, a yeast transcriptional activator that mediates multidrug resistance, regulates the metabolic stress response. EMBO J. 1994 Sep 1;13(17):4036–4041. [PMC free article] [PubMed]
  • Grant CM, Collinson LP, Roe JH, Dawes IW. Yeast glutathione reductase is required for protection against oxidative stress and is a target gene for yAP-1 transcriptional regulation. Mol Microbiol. 1996 Jul;21(1):171–179. [PubMed]
  • Haase E, Servos J, Brendel M. Isolation and characterization of additional genes influencing resistance to various mutagens in the yeast Saccharomyces cerevisiae. Curr Genet. 1992 Apr;21(4-5):319–324. [PubMed]
  • Harshman KD, Moye-Rowley WS, Parker CS. Transcriptional activation by the SV40 AP-1 recognition element in yeast is mediated by a factor similar to AP-1 that is distinct from GCN4. Cell. 1988 Apr 22;53(2):321–330. [PubMed]
  • Hertle K, Haase E, Brendel M. The SNQ3 gene of Saccharomyces cerevisiae confers hyper-resistance to several functionally unrelated chemicals. Curr Genet. 1991 Jun;19(6):429–433. [PubMed]
  • Hill DE, Hope IA, Macke JP, Struhl K. Saturation mutagenesis of the yeast his3 regulatory site: requirements for transcriptional induction and for binding by GCN4 activator protein. Science. 1986 Oct 24;234(4775):451–457. [PubMed]
  • Hinnebusch AG. Mechanisms of gene regulation in the general control of amino acid biosynthesis in Saccharomyces cerevisiae. Microbiol Rev. 1988 Jun;52(2):248–273. [PMC free article] [PubMed]
  • Hirata D, Yano K, Miyakawa T. Stress-induced transcriptional activation mediated by YAP1 and YAP2 genes that encode the Jun family of transcriptional activators in Saccharomyces cerevisiae. Mol Gen Genet. 1994 Feb;242(3):250–256. [PubMed]
  • Hope IA, Struhl K. GCN4 protein, synthesized in vitro, binds HIS3 regulatory sequences: implications for general control of amino acid biosynthetic genes in yeast. Cell. 1985 Nov;43(1):177–188. [PubMed]
  • Iyer V, Struhl K. Mechanism of differential utilization of the his3 TR and TC TATA elements. Mol Cell Biol. 1995 Dec;15(12):7059–7066. [PMC free article] [PubMed]
  • Iyer V, Struhl K. Absolute mRNA levels and transcriptional initiation rates in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5208–5212. [PMC free article] [PubMed]
  • Kamada Y, Jung US, Piotrowski J, Levin DE. The protein kinase C-activated MAP kinase pathway of Saccharomyces cerevisiae mediates a novel aspect of the heat shock response. Genes Dev. 1995 Jul 1;9(13):1559–1571. [PubMed]
  • Kamens J, Richardson P, Mosialos G, Brent R, Gilmore T. Oncogenic transformation by vrel requires an amino-terminal activation domain. Mol Cell Biol. 1990 Jun;10(6):2840–2847. [PMC free article] [PubMed]
  • Karin M. The regulation of AP-1 activity by mitogen-activated protein kinases. J Biol Chem. 1995 Jul 14;270(28):16483–16486. [PubMed]
  • Kim J, Struhl K. Determinants of half-site spacing preferences that distinguish AP-1 and ATF/CREB bZIP domains. Nucleic Acids Res. 1995 Jul 11;23(13):2531–2537. [PMC free article] [PubMed]
  • Kim J, Tzamarias D, Ellenberger T, Harrison SC, Struhl K. Adaptability at the protein-DNA interface is an important aspect of sequence recognition by bZIP proteins. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4513–4517. [PMC free article] [PubMed]
  • Klein C, Struhl K. Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity. Mol Cell Biol. 1994 Mar;14(3):1920–1928. [PMC free article] [PubMed]
  • König P, Richmond TJ. The X-ray structure of the GCN4-bZIP bound to ATF/CREB site DNA shows the complex depends on DNA flexibility. J Mol Biol. 1993 Sep 5;233(1):139–154. [PubMed]
  • Kuge S, Jones N. YAP1 dependent activation of TRX2 is essential for the response of Saccharomyces cerevisiae to oxidative stress by hydroperoxides. EMBO J. 1994 Feb 1;13(3):655–664. [PMC free article] [PubMed]
  • Kuge S, Jones N, Nomoto A. Regulation of yAP-1 nuclear localization in response to oxidative stress. EMBO J. 1997 Apr 1;16(7):1710–1720. [PMC free article] [PubMed]
  • Kumada K, Yanagida M, Toda T. Caffeine-resistance in fission yeast is caused by mutations in a single essential gene, crm1+. Mol Gen Genet. 1996 Jan 15;250(1):59–68. [PubMed]
  • Kuras L, Cherest H, Surdin-Kerjan Y, Thomas D. A heteromeric complex containing the centromere binding factor 1 and two basic leucine zipper factors, Met4 and Met28, mediates the transcription activation of yeast sulfur metabolism. EMBO J. 1996 May 15;15(10):2519–2529. [PMC free article] [PubMed]
  • Landschulz WH, Johnson PF, McKnight SL. The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science. 1988 Jun 24;240(4860):1759–1764. [PubMed]
  • Marchler G, Schüller C, Adam G, Ruis H. A Saccharomyces cerevisiae UAS element controlled by protein kinase A activates transcription in response to a variety of stress conditions. EMBO J. 1993 May;12(5):1997–2003. [PMC free article] [PubMed]
  • Miyahara K, Hirata D, Miyakawa T. yAP-1- and yAP-2-mediated, heat shock-induced transcriptional activation of the multidrug resistance ABC transporter genes in Saccharomyces cerevisiae. Curr Genet. 1996 Jan;29(2):103–105. [PubMed]
  • Moye-Rowley WS, Harshman KD, Parker CS. Yeast YAP1 encodes a novel form of the jun family of transcriptional activator proteins. Genes Dev. 1989 Mar;3(3):283–292. [PubMed]
  • Nehlin JO, Carlberg M, Ronne H. Yeast SKO1 gene encodes a bZIP protein that binds to the CRE motif and acts as a repressor of transcription. Nucleic Acids Res. 1992 Oct 25;20(20):5271–5278. [PMC free article] [PubMed]
  • Nojima H, Leem SH, Araki H, Sakai A, Nakashima N, Kanaoka Y, Ono Y. Hac1: a novel yeast bZIP protein binding to the CRE motif is a multicopy suppressor for cdc10 mutant of Schizosaccharomyces pombe. Nucleic Acids Res. 1994 Dec 11;22(24):5279–5288. [PMC free article] [PubMed]
  • Oliphant AR, Brandl CJ, Struhl K. Defining the sequence specificity of DNA-binding proteins by selecting binding sites from random-sequence oligonucleotides: analysis of yeast GCN4 protein. Mol Cell Biol. 1989 Jul;9(7):2944–2949. [PMC free article] [PubMed]
  • Oliviero S, Robinson GS, Struhl K, Spiegelman BM. Yeast GCN4 as a probe for oncogenesis by AP-1 transcription factors: transcriptional activation through AP-1 sites is not sufficient for cellular transformation. Genes Dev. 1992 Sep;6(9):1799–1809. [PubMed]
  • Oliviero S, Struhl K. Synergistic transcriptional enhancement does not depend on the number of acidic activation domains bound to the promoter. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):224–228. [PMC free article] [PubMed]
  • O'Shea EK, Klemm JD, Kim PS, Alber T. X-ray structure of the GCN4 leucine zipper, a two-stranded, parallel coiled coil. Science. 1991 Oct 25;254(5031):539–544. [PubMed]
  • Polley SD, Caddick MX. Molecular characterisation of meaB, a novel gene affecting nitrogen metabolite repression in Aspergillus nidulans. FEBS Lett. 1996 Jun 17;388(2-3):200–205. [PubMed]
  • Ponticelli AS, Pardee TS, Struhl K. The glutamine-rich activation domains of human Sp1 do not stimulate transcription in Saccharomyces cerevisiae. Mol Cell Biol. 1995 Feb;15(2):983–988. [PMC free article] [PubMed]
  • Pu WT, Struhl K. Highly conserved residues in the bZIP domain of yeast GCN4 are not essential for DNA binding. Mol Cell Biol. 1991 Oct;11(10):4918–4926. [PMC free article] [PubMed]
  • Pu WT, Struhl K. The leucine zipper symmetrically positions the adjacent basic regions for specific DNA binding. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):6901–6905. [PMC free article] [PubMed]
  • Ransone LJ, Verma IM. Nuclear proto-oncogenes fos and jun. Annu Rev Cell Biol. 1990;6:539–557. [PubMed]
  • Schnell N, Entian KD. Identification and characterization of a Saccharomyces cerevisiae gene (PAR1) conferring resistance to iron chelators. Eur J Biochem. 1991 Sep 1;200(2):487–493. [PubMed]
  • Schnell N, Krems B, Entian KD. The PAR1 (YAP1/SNQ3) gene of Saccharomyces cerevisiae, a c-jun homologue, is involved in oxygen metabolism. Curr Genet. 1992 Apr;21(4-5):269–273. [PubMed]
  • Sellers JW, Vincent AC, Struhl K. Mutations that define the optimal half-site for binding yeast GCN4 activator protein and identify an ATF/CREB-like repressor that recognizes similar DNA sites. Mol Cell Biol. 1990 Oct;10(10):5077–5086. [PMC free article] [PubMed]
  • Struhl K. The DNA-binding domains of the jun oncoprotein and the yeast GCN4 transcriptional activator protein are functionally homologous. Cell. 1987 Sep 11;50(6):841–846. [PubMed]
  • Struhl K. The JUN oncoprotein, a vertebrate transcription factor, activates transcription in yeast. Nature. 1988 Apr 14;332(6165):649–650. [PubMed]
  • Struhl K. Reverse biochemistry: methods and applications for synthesizing yeast proteins in vitro. Methods Enzymol. 1991;194:520–535. [PubMed]
  • Tanaka K, Matsumoto K, Toh-e A. Dual regulation of the expression of the polyubiquitin gene by cyclic AMP and heat shock in yeast. EMBO J. 1988 Feb;7(2):495–502. [PMC free article] [PubMed]
  • Toda T, Shimanuki M, Yanagida M. Fission yeast genes that confer resistance to staurosporine encode an AP-1-like transcription factor and a protein kinase related to the mammalian ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases. Genes Dev. 1991 Jan;5(1):60–73. [PubMed]
  • Toda T, Uno I, Ishikawa T, Powers S, Kataoka T, Broek D, Cameron S, Broach J, Matsumoto K, Wigler M. In yeast, RAS proteins are controlling elements of adenylate cyclase. Cell. 1985 Jan;40(1):27–36. [PubMed]
  • Turi TG, Webster P, Rose JK. Brefeldin A sensitivity and resistance in Schizosaccharomyces pombe. Isolation of multiple genes conferring resistance. J Biol Chem. 1994 Sep 30;269(39):24229–24236. [PubMed]
  • Tzamarias D, Struhl K. Functional dissection of the yeast Cyc8-Tup1 transcriptional co-repressor complex. Nature. 1994 Jun 30;369(6483):758–761. [PubMed]
  • Velculescu VE, Zhang L, Zhou W, Vogelstein J, Basrai MA, Bassett DE, Jr, Hieter P, Vogelstein B, Kinzler KW. Characterization of the yeast transcriptome. Cell. 1997 Jan 24;88(2):243–251. [PubMed]
  • Vincent AC, Struhl K. ACR1, a yeast ATF/CREB repressor. Mol Cell Biol. 1992 Dec;12(12):5394–5405. [PMC free article] [PubMed]
  • Wemmie JA, Szczypka MS, Thiele DJ, Moye-Rowley WS. Cadmium tolerance mediated by the yeast AP-1 protein requires the presence of an ATP-binding cassette transporter-encoding gene, YCF1. J Biol Chem. 1994 Dec 23;269(51):32592–32597. [PubMed]
  • Wu A, Wemmie JA, Edgington NP, Goebl M, Guevara JL, Moye-Rowley WS. Yeast bZip proteins mediate pleiotropic drug and metal resistance. J Biol Chem. 1993 Sep 5;268(25):18850–18858. [PubMed]
  • Wu AL, Moye-Rowley WS. GSH1, which encodes gamma-glutamylcysteine synthetase, is a target gene for yAP-1 transcriptional regulation. Mol Cell Biol. 1994 Sep;14(9):5832–5839. [PMC free article] [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Gene
    Gene
    Gene links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • MedGen
    MedGen
    Related information in MedGen
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links
  • Taxonomy
    Taxonomy
    Related taxonomy entry
  • Taxonomy Tree
    Taxonomy Tree

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...