Metal-sensing transcription factors Mac1p and Aft1p coordinately regulate vacuolar copper transporter CTR2 in Saccharomyces cerevisiae.

CTR2 encodes a low-affinity copper transporter that mediates the mobilization of vacuolar copper stores in yeast. We previously reported that CTR2 can be upregulated by copper deficiency via copper-sensing transcription factor Mac1p. In the present study, we found that iron depletion also induces the transcription of CTR2. The upregulation of CTR2 induced by iron depletion was abrogated by the genetic deletion of either Mac1p or iron-sensing transcription factor Aft1p. The ablation of either MAC1 or AFT1 also abrogated CTR2 expression induced by copper depletion. Our further study revealed that exogenous Aft1p upregulates CTR2 transcription only in the presence of Mac1p, whereas exogenous Mac1p upregulates CTR2 transcription only in the presence of Aft1p. Exogenous Mac1p and Aft1p form a stable complex and synergistically enhance CTR2 transcription. These data suggest that Aft1p and Mac1p might corporately regulate transcription of CTR2.