1sse

Structural highlights

Function

AP1_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. Preferentially binds to promoters with the core binding site 5'-TTA[CG]TAA-3'. Activity of the transcription factor 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. Activation by hydrogen peroxide or thiol-reactive chemicals elicit distinct adaptive gene responses. 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] [14] [15] [16] [17]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ 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
2. ↑ 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
3. ↑ 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
4. ↑ 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
5. ↑ Cohen BA, Pilpel Y, Mitra RD, Church GM. Discrimination between paralogs using microarray analysis: application to the Yap1p and Yap2p transcriptional networks. Mol Biol Cell. 2002 May;13(5):1608-14. PMID:12006656 doi:10.1091/mbc.01-10-0472
6. ↑ 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
7. ↑ 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
8. ↑ 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
9. ↑ 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
10. ↑ 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
11. ↑ 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):269-73. PMID:1525853 doi:10.1007/BF00351681
12. ↑ Ouyang X, Tran QT, Goodwin S, Wible RS, Sutter CH, Sutter TR. Yap1 activation by H2O2 or thiol-reactive chemicals elicits distinct adaptive gene responses. Free Radic Biol Med. 2011 Jan 1;50(1):1-13. PMID:20971184 doi:10.1016/j.freeradbiomed.2010.10.697
13. ↑ 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
14. ↑ Wemmie JA, Steggerda SM, Moye-Rowley WS. The Saccharomyces cerevisiae AP-1 protein discriminates between oxidative stress elicited by the oxidants H2O2 and diamide. J Biol Chem. 1997 Mar 21;272(12):7908-14. PMID:9065458 doi:10.1074/jbc.272.12.7908
15. ↑ 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
16. ↑ 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
17. ↑ 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