cDNA microarray analysis indicated that mRNA levels of Fit2p and Fit3p, proteins involved in iron retention within the yeast cell wall, were markedly increased by treatment of Saccharomyces cerevisiae with cisplatin. Expression of FIT2 and FIT3 is known to be transcriptionally regulated by Aft1p. Northern blotting demonstrated a time- and concentration-dependent increase in the mRNA levels of both proteins following treatment with cisplatin. However, overexpression or disruption of the FIT2 or FIT3 genes had little effect on the susceptibility of yeast to cisplatin. Although Fit2p and Fit3p do not appear to be directly involved in protecting against the toxic effects of cisplatin, the present results suggest the existence of an activation system of gene expression in response to cisplatin within yeast cells.
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