Yap8p activation in Saccharomyces cerevisiae under arsenic conditions

Abstract

Yap8p, a member of the Saccharomyces cerevisiae Yap family, is activated in response to arsenic. Both the mechanisms by which this activation takes place and its regulation have not yet been identified. In this report, we show that Yap8p is not activated at the transcriptional level but, rather, its nuclear transport is actively regulated and dependent on the exportin chromosome region maintenance protein. In addition, it is shown that Cys 132 , Cys 137 and Cys 274 are essential for Yap8p localization and transactivation function both of which are required for its biological activity.

The Yap family and its role in stress response

“…Under stress conditions, As(III) modifies the sulphydryl groups of specific cysteine on both proteins (our unpublished data), masking the NES and preventing recognition by the exportin Crm1. Arsenic modification of Yap8 involves Cys132, 137 and 274, whereas Yap1 modification occurs in the Cys residues located in the c-CRD (Figure 1) [67]. In contrast to this view, it was described [68] that Yap8 is a nuclear-resident protein and that Cys132 and 274 do not affect Figure 3.…”

“…Yap8 is the master regulator of this response, mediating transcriptional activation of ACR2 and ACR3, encoding the arsenate-reductase and the plasma membrane arsenite-efflux protein, respectively [67,68]. Both proteins constitute a first-line defence, since they facilitate the extrusion of arsenite molecules from the cytoplasm.…”

“…In the mutant yap8, which accumulates high levels of As(III), the well-known Yap1 target genes TRX2, GSH1 and SOD1 are even more induced compared to the wild-type strain, suggesting that arsenite retention in the cytoplasm triggers a more severe antioxidant response. Thus, Yap1 is essential to promote cell adaptation by preventing the accumulation of the very toxic reactive oxygen species (ROS) generated by arsenic compounds (Figure 3) [67]. The upregulation of cell antioxidant defences by arsenic compounds is strongly corroborated by high-throughput arsenite/arsenate-triggered changes in transcriptional profiling ( [67,70]; Amaral et al, unpublished work).…”

“…Thus, Yap1 is essential to promote cell adaptation by preventing the accumulation of the very toxic reactive oxygen species (ROS) generated by arsenic compounds (Figure 3) [67]. The upregulation of cell antioxidant defences by arsenic compounds is strongly corroborated by high-throughput arsenite/arsenate-triggered changes in transcriptional profiling ( [67,70]; Amaral et al, unpublished work).…”

“…Under physiological conditions, the chimeras GFP-Yap1 and GFP-Yap8 shuttle between the nucleus and the cytoplasm, rapidly accumulating in the nucleus after exposure to arsenic [67]. Subcellular compartmentalization of both proteins is mediated through the binding of Crm1 to the nuclear export signal (NES) domain under physiological growth.…”