COPPER DIFFERENTIALLY REGULATES THE ACTIVITY AND DEGRADATION OF YEASTMAC1 TRANSCRIPTION FACTOR

Copper is an essential metal ion that is toxic when accumulated to hig h intracellular concentrations. The yeast Mad protein is a copper-sens ing transcription factor that is essential for both the activation and inactivation of genes required for high affinity copper ion transport . Here we demonstrate that in response to low copper ion concentration s Mac1 protein is rendered inactive for copper transporter gene transc ription. Under high copper ion concentrations Mac1 is degraded in a ra pid, copper-specific manner. This degradation is critical to prevent c opper toxicity that would otherwise result from sustained expression o f the copper transport genes. These results demonstrate that nutrition al and toxic copper concentrations elicit distinct fates for the Mad c opper-sensing transcription factor and establish a new mechanism by wh ich trace metals regulate gene expression.