| Structural highlights
1sse is a 2 chain structure with sequence from Atcc 18824. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Gene: | YAP1, SNQ3, PAR1, PDR4, YML007W, YM9571.12 (ATCC 18824) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[YAP1_YEAST] Transcription activator involved in oxidative stress response and redox homeostasis. Regulates the transcription of genes encoding antioxidant enzymes and components of the cellular thiol-reducing pathways, including the thioredoxin system (TRX2, TRR1), the glutaredoxin system (GSH1, GLR1), superoxide dismutase (SOD1, SOD2), glutathione peroxidase (GPX2), and thiol-specific peroxidases (TSA1, AHP1). The induction of some of these genes requires the cooperative action of both, YAP1 and SKN7. YAP1 preferentially binds to promoters with the core binding site 5'-TTA[CG]TAA-3'. Activity of YAP1 is controlled through oxidation of specific cysteine residues resulting in the alteration of its subcellular location. Oxidative stress (as well as carbon stress, but not increased temperature, acidic pH, or ionic stress) induces nuclear accumulation and as a result YAP1 transcriptional activity. Nuclear export is restored when disulfide bonds are reduced by thioredoxin (TRX2), whose expression is controlled by YAP1, providing a mechanism for negative autoregulation. When overexpressed, YAP1 confers pleiotropic drug-resistance and increases cellular tolerance to cadmium, iron chelators and zinc.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The ability of organisms to alter their gene expression patterns in response to environmental changes is essential for viability. A central regulator of the response to oxidative stress in Saccharomyces cerevisiae is the Yap1 transcription factor. Upon activation by increased levels of reactive oxygen species, Yap1 rapidly redistributes to the nucleus where it regulates the expression of up to 70 genes. Here we identify a redox-regulated domain of Yap1 and determine its high-resolution solution structure. In the active oxidized form, a nuclear export signal (NES) in the carboxy-terminal cysteine-rich domain is masked by disulphide-bond-mediated interactions with a conserved amino-terminal alpha-helix. Point mutations that weaken the hydrophobic interactions between the N-terminal alpha-helix and the C-terminal NES-containing domain abolished redox-regulated changes in subcellular localization of Yap1. Upon reduction of the disulphide bonds, Yap1 undergoes a change to an unstructured conformation that exposes the NES and allows redistribution to the cytoplasm. These results reveal the structural basis of redox-dependent Yap1 localization and provide a previously unknown mechanism of transcription factor regulation by reversible intramolecular disulphide bond formation.
Structural basis for redox regulation of Yap1 transcription factor localization.,Wood MJ, Storz G, Tjandra N Nature. 2004 Aug 19;430(7002):917-21. PMID:15318225[14]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wemmie JA, Wu AL, Harshman KD, Parker CS, Moye-Rowley WS. Transcriptional activation mediated by the yeast AP-1 protein is required for normal cadmium tolerance. J Biol Chem. 1994 May 20;269(20):14690-7. PMID:8182076
- ↑ Fernandes L, Rodrigues-Pousada C, Struhl K. Yap, a novel family of eight bZIP proteins in Saccharomyces cerevisiae with distinct biological functions. Mol Cell Biol. 1997 Dec;17(12):6982-93. PMID:9372930
- ↑ Yan C, Lee LH, Davis LI. Crm1p mediates regulated nuclear export of a yeast AP-1-like transcription factor. EMBO J. 1998 Dec 15;17(24):7416-29. PMID:9857197 doi:http://dx.doi.org/10.1093/emboj/17.24.7416
- ↑ Vilela C, Linz B, Rodrigues-Pousada C, McCarthy JE. The yeast transcription factor genes YAP1 and YAP2 are subject to differential control at the levels of both translation and mRNA stability. Nucleic Acids Res. 1998 Mar 1;26(5):1150-9. PMID:9469820
- ↑ Lee J, Godon C, Lagniel G, Spector D, Garin J, Labarre J, Toledano MB. Yap1 and Skn7 control two specialized oxidative stress response regulons in yeast. J Biol Chem. 1999 Jun 4;274(23):16040-6. PMID:10347154
- ↑ Delaunay A, Isnard AD, Toledano MB. H2O2 sensing through oxidation of the Yap1 transcription factor. EMBO J. 2000 Oct 2;19(19):5157-66. PMID:11013218 doi:http://dx.doi.org/10.1093/emboj/19.19.5157
- ↑ Isoyama T, Murayama A, Nomoto A, Kuge S. 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. J Biol Chem. 2001 Jun 15;276(24):21863-9. Epub 2001 Mar 23. PMID:11274141 doi:http://dx.doi.org/10.1074/jbc.M009258200
- ↑ Kuge S, Arita M, Murayama A, Maeta K, Izawa S, Inoue Y, Nomoto A. Regulation of the yeast Yap1p nuclear export signal is mediated by redox signal-induced reversible disulfide bond formation. Mol Cell Biol. 2001 Sep;21(18):6139-50. PMID:11509657
- ↑ Delaunay A, Pflieger D, Barrault MB, Vinh J, Toledano MB. A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation. Cell. 2002 Nov 15;111(4):471-81. PMID:12437921
- ↑ Wiatrowski HA, Carlson M. Yap1 accumulates in the nucleus in response to carbon stress in Saccharomyces cerevisiae. Eukaryot Cell. 2003 Feb;2(1):19-26. PMID:12582119
- ↑ Wood MJ, Andrade EC, Storz G. The redox domain of the Yap1p transcription factor contains two disulfide bonds. Biochemistry. 2003 Oct 21;42(41):11982-91. PMID:14556629 doi:http://dx.doi.org/10.1021/bi035003d
- ↑ Azevedo D, Tacnet F, Delaunay A, Rodrigues-Pousada C, Toledano MB. Two redox centers within Yap1 for H2O2 and thiol-reactive chemicals signaling. Free Radic Biol Med. 2003 Oct 15;35(8):889-900. PMID:14556853
- ↑ Veal EA, Ross SJ, Malakasi P, Peacock E, Morgan BA. Ybp1 is required for the hydrogen peroxide-induced oxidation of the Yap1 transcription factor. J Biol Chem. 2003 Aug 15;278(33):30896-904. Epub 2003 May 12. PMID:12743123 doi:http://dx.doi.org/10.1074/jbc.M303542200
- ↑ Wood MJ, Storz G, Tjandra N. Structural basis for redox regulation of Yap1 transcription factor localization. Nature. 2004 Aug 19;430(7002):917-21. PMID:15318225 doi:http://dx.doi.org/10.1038/nature02790
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