Journal of Biological Chemistry
Volume 276, Issue 36, 7 September 2001, Pages 34221-34226
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GENES: STRUCTURE AND REGULATION
Aft2p, a Novel Iron-regulated Transcription Activator That Modulates, with Aft1p, Intracellular Iron Use and Resistance to Oxidative Stress in Yeast*

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The yeast, Saccharomyces cerevisiae,contains a transcription activator, Aft1p, that regulates the transcription of the high affinity iron transport system genes. This report describes the properties of Aft2p, a protein 39% homologous to Aft1p. Aft2p was found to activate transcription. Overproduction of Aft2p activates the transcription of theAFT1 target gene FET3. The doubleaft1aft2 mutant was unable to grow in iron-deprived conditions. Because a fet3 mutant does not show this deficiency, the defect is not solely caused by mis-regulation of iron transport but also involves defective iron use by the cells. Theaft1 cells were unable to grow in aerobic conditions on plates containing raffinose as the sole carbon source. The inability to grow on raffinose is not caused by the cell iron content being too low to sustain respiratory metabolism, because the oxygen consumption ofaft1 mutants showed that their respiratory activity is 2-fold higher than that of controls. The double aft1aft2mutant also has many phenotypes related to oxidative stress such as H2O2 hypersensitivity, oxygen-dependent copper toxicity, and oxygen-dependent methionine auxotrophy, which are suppressed in anaerobiosis. These results suggest that Aft2p and Aft1p have overlapping roles in the control of iron-regulated pathway(s) connected to oxidative stress resistance in yeast.

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Published, JBC Papers in Press, July 11, 2001, DOI 10.1074/jbc.M104987200

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This work was supported by grants from the Ministère de la Recherche (Program de Recherches Fondamentales en Microbiologie, Maladies Infectieuses et Parasitaires) and the Association pour la Recherche sur le Cancer (ARC 5439).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.