Aft2p, a novel iron-regulated transcription activator that modulates, withAft1p, intracellular iron use and resistance to oxidative stress in yeast.

The yeast, Saccharomyces cerevisiae, contains a transcription activator, Af t1p, that regulates the transcription of the high affinity iron transport s ystem genes. This report describes the properties of Aft2p, a protein 39% h omologous to Aft1p. Aft2p was found to activate transcription. Overproducti on of Aft2p activates the transcription of the AFT1 target gene FET3. The d ouble aft1aft2 mutant was unable to grow in iron-deprived conditions. Becau se a fet3 mutant does not show this deficiency, the defect is not solely ca used by mis-regulation of iron transport but also involves defective iron u se by the cells. The aft1 cells were unable to grow in aerobic conditions o n plates containing raffinose as the sole carbon source. The inability to g row on raffinose is not caused by the cell iron content being too low to su stain respiratory metabolism, because the oxygen consumption of aft1 mutant s showed that their respiratory activity is 2-fold higher than that of cont rols. The double aft1aft2 mutant also has many phenotypes related to oxidat ive stress such as H2O2 hypersensitivity, oxygen-dependent copper toxicity, and oxygen-dependent methionine auxotrophy, which are suppressed in anaero biosis. These results suggest that Aft2p and Aft1p have overlapping roles i n the control of iron-regulated pathway(s) connected to oxidative stress re sistance in yeast.