Involvement of the cell wall integrity pathway in protection against cadmium and arsenate stresses in Saccharomyces cerevisiae.

Contamination of soil and water with heavy metals and metalloids is one of serious environmental problems. Cadmium and arsenic are major environmental contaminants that pose a serious threat to human health. Although toxicities of cadmium and arsenic to living organisms have been extensively studied, molecular mechanisms of cellular response to cadmium and arsenic remain poorly understood. In this study, we demonstrate that the cell wall integrity (CWI) pathway is involved in coping with cell wall stresses induced by cadmium and arsenate through its role in the regulation of cell wall modification. Interestingly, the Rlm1p and SBF (Swi4p-Swi6p) transcription factors of the CWI pathway were specifically required for tolerances to cadmium and arsenate, respectively. Furthermore, we found that PIR2 gene encoding cell wall O-mannosylated heat shock protein, whose expression is under the control of the CWI pathway, is important for maintaining cell wall integrity during cadmium and arsenate stresses. In addition, our results revealed that the CWI pathway is involved in modulating the expression of genes involved in cell wall biosynthesis and cell cycle control in response to cadmium and arsenate via distinct sets of transcriptional regulators.IMPORTANCE Environmental pollution by metal/metalloid such as cadmium and arsenic has become a serious problem in many countries, especially in developing countries. This study shows that, in yeast S. cerevisiae, the CWI pathway plays a protective role against cadmium and arsenate through the upregulation of genes involved in cell wall biosynthesis and cell cycle control, possibly in order to modulate cell wall reconstruction and cell cycle phase transition, respectively. These data provide insights into molecular mechanisms underlying adaptive response to cadmium and arsenate.