## 1 Introduction  
Cells defend themselves against oxidative stress by having oxidation-sensitive proteins, which, when triggered, lead to the expression of antioxidant genes. The oxidative stress response in yeast is coordinated by the oxidation-sensitive Yap1p transcription factor, which upon oxidation of critical cysteine thiols, accumulates in the nucleus and transcribes antioxidant phase II genes [1]. Electrophilic alkylating agents such as the phytochemical allicin or the xenobiotic _N_-ethylmaleimide oxidize C-term cysteines in Yap1p. In contrast, H2O2, working in conjunction with Gpx3p and Ybp1p, causes intramolecular folding by internal disulfide bridge formation between N- and C-term cysteinesin Yap1p. In both cases, the nuclear export protein binding site becomes masked, causing Yap1p to accumulate in the nucleus, thus enabling it to transcribe target genes [2; 3]. In the course of our work with the sulfur-containing electrophile allicin (diallylithiosulfinate) that is produced as a defense substance by garlic (_Allium sativum_) upon tissue injury [4], we developed a reporter system for Yap1p activation by fusing the Yap1p-dependent promoter of the YKL071w open reading frame to a luciferase coding sequence [3]. A broad spectrum of oxidative and thiol-reactive substances induce the YKL071w gene, for example, allicin (27-fold) [5], the mycotoxin patulin (253-fold) [6], the phytochemical clastrol (31-fold) [7] and the pentose degradation product furfural (7-fold) [8]. We gave _YKL071w_ the working name oxidative stress-induced1 (_OSII_) [3]. Allicin has been shown to activate the Kaep1-Nrf2/ARE system that, in mammalian cells, perceives electrophilic oxidants, and coordinates the OSR [9; 10; 11]. Kaep1 (Kelch-like ECH-associated protein) in its reduced state has free cysteine thiols and associates with the transcription factor Nrf2, targeting it for ubiquitination and degradation in the cytosol. However, when the cysteine thiols in Kaep1 are alkylated by electrophiles, Kaep1 dissociates from Nrf2, which is thus stabilized and transported to the nucleus, where it associates with the co-transcription factor Maf and facilitates transcription of antioxidant phase II genes that have an antioxidant response element (ARE) in their promoter [12]. Reporter systems based on the Kaep1-Nrf2/ARE response have been used to detect potentially useful electrophilic or pro-electrophilic drugs that activate phase II protective enzymes, and thus work physiologically as antioxidants [13]. For example, using ARE reporter systems, certain cancer chemotherapeutic agents were demonstrated to activate Nrf2 [14], and in the context of the role of oxidative stress in neurodegenerative disorders, various botanicals were shown to exert a protective effect via activation of ARE-regulated genes in astrocytes [15]. Another example is the LuSens assay system employing a human keratinocyte cell line transfected with an ARE::luciferase construct, which was developed to test for undesirable skin-sensitizing substances in response to EU legislation banning animal testing for cosmetic products [16; 17]. In assays using the Kaep1-Nrf2/ARE system, the phytochemical sulforaphene is usually employed as a positive control because it alkylates Kaep1 efficiently and results in a large ARE-dependent response. Sulforaphene, alone or in combination with other substances, has been used to combat oxidative stress and reduce inflammation [18; 19]. Because KEAP1 and Yap1 are both activated by the same chemical mechanisms, logically, if an electrophilic oxidant reacts with the sensitive cysteines in Yap1, it will most likely react chemically with the sensitive cysteines in Kaep1, because in both systems these reactive cysteines have evolved to detect oxidative stress and coordinate the oxidative stress responses in their respective hosts. Indeed, very many such substances have already been independently shown to trigger both the Kaep1 and Yap1 systems (Table 1).