YAP1/YML007W Summary Help

Standard Name YAP1 1
Systematic Name YML007W
Alias PAR1 , SNQ3
Feature Type ORF, Verified
Description Basic leucine zipper (bZIP) transcription factor; required for oxidative stress tolerance; activated by H2O2 through the multistep formation of disulfide bonds and transit from the cytoplasm to the nucleus; Yap1p is degraded in the nucleus after the oxidative stress has passed; mediates resistance to cadmium; YAP1 has a paralog, CAD1, that arose from the whole genome duplication; relative distribution to the nucleus increases upon DNA replication stress (2, 3, 4, 5, 6, 7, 8 and see Summary Paragraph)
Name Description Yeast AP-1 2
Chromosomal Location
ChrXIII:253848 to 255800 | ORF Map | GBrowse
Gbrowse
Genetic position: -8 cM
Gene Ontology Annotations All YAP1 GO evidence and references
  View Computational GO annotations for YAP1
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
High-throughput
Cellular Component
Manually curated
High-throughput
Regulatory Role
Binding motifs Predicted YAP1 Binding Site Locations
    Regulatory modules predicted: stressResponse (493)
    Resources
    Mutant phenotypes All YAP1 Phenotype evidence and references
    Classical genetics
    gain of function
    null
    overexpression
    Large-scale survey
    null
    overexpression
    Resources
    interactions All YAP1 Interaction evidence and references
    272 total interaction(s) for 171 unique genes/features.
    Physical Interactions
    • Affinity Capture-MS: 73
    • Affinity Capture-RNA: 2
    • Affinity Capture-Western: 10
    • Biochemical Activity: 5
    • PCA: 2
    • Reconstituted Complex: 8
    • Two-hybrid: 32
    Genetic Interactions
    • Dosage Growth Defect: 2
    • Dosage Lethality: 1
    • Dosage Rescue: 9
    • Negative Genetic: 79
    • Phenotypic Enhancement: 11
    • Phenotypic Suppression: 1
    • Positive Genetic: 6
    • Synthetic Growth Defect: 24
    • Synthetic Lethality: 2
    • Synthetic Rescue: 5
    Resources
    Expression Summary
    histogram
    Resources
    Protein Information All YAP1 Protein evidence and references
    Localization
    Phosphorylation PhosphoGRID | PhosphoPep Database
    Structure
    Homologs
    sequence information
    ChrXIII:253848 to 255800 | ORF Map | GBrowse
    SGD ORF map
    Genetic position: -8 cM
    Last Update Coordinates: 1996-07-31 | Sequence: 1996-07-31
    Subfeature details
    Relative
    Coordinates    		 Chromosomal
    Coordinates    		 Most Recent Updates
    Coordinates Sequence
    CDS 1..1953 253848..255800 1996-07-31 1996-07-31
    Retrieve sequences
    Analyze Sequence
    S288C only
    S288C vs. other species
    S288C vs. other strains
    Resources
    External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
    Primary SGDIDS000004466
    SUMMARY PARAGRAPH for YAP1

    Yap1p, a member of the AP-1 family of transcription factors, activates the transcription of anti-oxidant genes in response to oxidative stress (reviewed in 9, 10). Yap1p is involved in one of three mechanisms that regulate the transcriptional response to oxidative stress. The other two involve Hog1p and Skn7p (reviewed in 11). The preferred Yap1p binding site is TTACTAA (12). The genes regulated by Yap1p include anti-oxidant genes such as TRR1, TRX2, GSH1, and GLR1 (13, 14, 15). Although many of the genes regulated by Yap1p are also regulated by Skn7p, Yap1p and Skn7p appear to respond to different oxidative stresses (15, 16). Consistent with its primary role in responding to oxidative stress, a yap1 null mutant is sensitive to multiple oxidative stresses, including hydrogen peroxide and compounds that alter the redox status in the cell (17, 18, 19).

    The transcriptional activity of Yap1p is regulated by its cellular localization (4, 20). The N-terminal region contains a nuclear localization signal (NLS) while the C-terminal region contains a nuclear export signal (NES) (4). In the absence of oxidative stress, Yap1p is exported from the nucleus via Crm1p, an exportin (21, 22). However, in the presence of hydrogen peroxide, Hyr1p, a protein similar to glutathione peroxidase, catalyzes the formation of an intramolecular disulfide bond in Yap1p (23). This conformational change allows Yap1p to accumulate in the nucleus (20). It has also been proposed that there are multiple mechanisms for activating Yap1p since exposure to diamide causes nuclear accumulation without the formation of this disulfide bond (24).

    Yap1p is negatively regulated by the thioredoxin system and calcium. The thioredoxin system, consisting of thioredoxin reductase (endcoded by TRR1) and thioredoxin 2 (encoded by TRX2), reduces the disulfide bond that is required for the nuclear accumulation of Yap1p (25, 23, 26). Dephosphorylation and degradation of Yap1p appear to be regulated by calcineurin (27).

    Yap1p was identified by its ability to activate transcription from the mammalian AP-1 recognition element found in the SV40 promoter (28, 29). Functional orthologs of Yap1p have been identified in many eukaryotes, including S. pombe (30), C. glabrata (31), K. lactis (32), and A. thaliana (33). These proteins define a subset of the AP-1 family protein family because they share a cysteine rich domain (CRD) that contains conserved cysteine residues (9).

    S. cerevisiae Yap1p has also been used to study anti-oxidant properties of green tea extracts and epigallocatechin gallate (EGCG, a polyphenolic favonoid in green tea). Although promoted as anti-oxidants, they appear to produce hydrogen peroxide under certain conditions and promote the nuclear localization of Yap1p (34).

    Last updated: 2007-06-01

    References cited on this page View Complete Literature Guide for YAP1
    1) Preston, R. and Jones, E.  (1989) Personal Communication, Mortimer Map Edition 10
    2) Moye-Rowley WS, et al.  (1989) Yeast YAP1 encodes a novel form of the jun family of transcriptional activator proteins. Genes Dev 3(3):283-92
    3) Wu A, et al.  (1993) Yeast bZip proteins mediate pleiotropic drug and metal resistance. J Biol Chem 268(25):18850-8
    4) Kuge S, et al.  (1997) Regulation of yAP-1 nuclear localization in response to oxidative stress. EMBO J 16(7):1710-20
    5) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
    6) Okazaki S, et al.  (2007) Multistep disulfide bond formation in Yap1 is required for sensing and transduction of H(2)O(2) stress signal. Mol Cell 27(4):675-88
    7) Gulshan K, et al.  (2012) Proteolytic degradation of the Yap1 transcription factor is regulated by subcellular localization and the E3 ubiquitin ligase Not4. J Biol Chem 287(32):26796-805
    8) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
    9) Toone WM and Jones N  (1999) AP-1 transcription factors in yeast. Curr Opin Genet Dev 9(1):55-61
    10) Temple MD, et al.  (2005) Complex cellular responses to reactive oxygen species. Trends Cell Biol 15(6):319-26
    11) Ikner A and Shiozaki K  (2005) Yeast signaling pathways in the oxidative stress response. Mutat Res 569(1-2):13-27
    12) Fernandes L, et al.  (1997) Yap, a novel family of eight bZIP proteins in Saccharomyces cerevisiae with distinct biological functions. Mol Cell Biol 17(12):6982-93
    13) Kuge S and Jones N  (1994) YAP1 dependent activation of TRX2 is essential for the response of Saccharomyces cerevisiae to oxidative stress by hydroperoxides. EMBO J 13(3):655-64
    14) Morgan BA, et al.  (1997) The Skn7 response regulator controls gene expression in the oxidative stress response of the budding yeast Saccharomyces cerevisiae. EMBO J 16(5):1035-44
    15) Lee J, et al.  (1999) Yap1 and Skn7 control two specialized oxidative stress response regulons in yeast. J Biol Chem 274(23):16040-6
    16) Brombacher K, et al.  (2006) The role of Yap1p and Skn7p-mediated oxidative stress response in the defence of Saccharomyces cerevisiae against singlet oxygen. Yeast 23(10):741-50
    17) Schnell N, et al.  (1992) The PAR1 (YAP1/SNQ3) gene of Saccharomyces cerevisiae, a c-jun homologue, is involved in oxygen metabolism. Curr Genet 21(4-5):269-73
    18) Wemmie JA, et al.  (1994) Transcriptional activation mediated by the yeast AP-1 protein is required for normal cadmium tolerance. J Biol Chem 269(20):14690-7
    19) Lopez-Mirabal HR, et al.  (2007) Cytoplasmic glutathione redox status determines survival upon exposure to the thiol-oxidant 4,4'-dipyridyl disulfide. FEMS Yeast Res 7(3):391-403
    20) Gulshan K, et al.  (2005) Oxidant-specific folding of Yap1p regulates both transcriptional activation and nuclear localization. J Biol Chem 280(49):40524-33
    21) Kuge S, et al.  (1998) Crm1 (XpoI) dependent nuclear export of the budding yeast transcription factor yAP-1 is sensitive to oxidative stress. Genes Cells 3(8):521-32
    22) Yan C, et al.  (1998) Crm1p mediates regulated nuclear export of a yeast AP-1-like transcription factor. EMBO J 17(24):7416-29
    23) Kuge S, et al.  (2001) Regulation of the yeast Yap1p nuclear export signal is mediated by redox signal-induced reversible disulfide bond formation. Mol Cell Biol 21(18):6139-50
    24) Delaunay A, et al.  (2000) H2O2 sensing through oxidation of the Yap1 transcription factor. EMBO J 19(19):5157-66
    25) Izawa S, et al.  (1999) Thioredoxin deficiency causes the constitutive activation of Yap1, an AP-1-like transcription factor in Saccharomyces cerevisiae. J Biol Chem 274(40):28459-65
    26) Carmel-Harel O, et al.  (2001) Role of thioredoxin reductase in the Yap1p-dependent response to oxidative stress in Saccharomyces cerevisiae. Mol Microbiol 39(3):595-605
    27) Yokoyama H, et al.  (2006) Involvement of calcineurin-dependent degradation of Yap1p in Ca(2+)-induced G(2) cell-cycle regulation in Saccharomyces cerevisiae. EMBO Rep 7(5):519-24
    28) Jones RH, et al.  (1988) Expression of the SV40 promoter in fission yeast: identification and characterization of an AP-1-like factor. Cell 53(4):659-67
    29) Harshman KD, et al.  (1988) 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 53(2):321-30
    30) Toda T, et al.  (1991) 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 5(1):60-73
    31) Chen KH, et al.  (2007) The bZip transcription factor Cgap1p is involved in multidrug resistance and required for activation of multidrug transporter gene CgFLR1 in Candida glabrata. Gene 386(1-2):63-72
    32) Billard P, et al.  (1997) Characterization of an AP-1-like transcription factor that mediates an oxidative stress response in Kluyveromyces lactis. Mol Gen Genet 257(1):62-70
    33) Babiychuk E, et al.  (1995) Arabidopsis thaliana NADPH oxidoreductase homologs confer tolerance of yeasts toward the thiol-oxidizing drug diamide. J Biol Chem 270(44):26224-31
    34) Maeta K, et al.  (2007) Green tea polyphenols function as prooxidants to activate oxidative-stress-responsive transcription factors in yeasts. Appl Environ Microbiol 73(2):572-80
    35) Zhu C, et al.  (2009) High-resolution DNA-binding specificity analysis of yeast transcription factors. Genome Res 19(4):556-66
    36) Harbison CT, et al.  (2004) Transcriptional regulatory code of a eukaryotic genome. Nature 431(7004):99-104
    37) Nguyen DT, et al.  (2001) Multiple Yap1p-binding sites mediate induction of the yeast major facilitator FLR1 gene in response to drugs, oxidants, and alkylating agents. J Biol Chem 276(2):1138-45