A copper-sensing transcription factor regulates iron uptake genes in Schizosaccharomyces pombe

Copper and iron serve essential functions as catalytic co-factors in a wide variety of critical cellular enzymes. Studies in yeast have demonstrated a n absolute dependence upon copper acquisition for proper assembly and funct ion of the iron transport machinery. We have cloned genes for a high affini ty copper transporter (Ctr4) and copper-sensing transcription factor (Cuf1) from Schizosaccharomyces pombe. Interestingly, the primary structure of Ct r4 and a putative human high affinity copper transport protein, hCtr1, sugg ests that they are derived from a fusion of the functionally redundant but structurally distinct Ctr1 and Ctr3 copper transporters from Saccharomyces cerevisiae. Furthermore, although Cuf1 activates ctr4(+) gene expression un der copper starvation conditions, under these same conditions Cuf1 directly represses expression of genes encoding components of the iron transport ma chinery. These studies have identified an evolutionary step in which copper transport modules have been fused, and describe a mechanism by which a cop per-sensing factor directly represses expression of the iron uptake genes u nder conditions in which the essential copper co-factor is scarce.