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Gene Review

AFT2  -  Aft2p

Saccharomyces cerevisiae S288c

Synonyms: Activator of iron transcription protein 2, Iron-regulated transcriptional activator AFT2, YPL202C
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High impact information on AFT2

  • Some of the AFT2-regulated genes are known to be regulated by Aft1p; however, AFT2-1(up)-dependent activation was independent of Aft1p [1].
  • A mutant allele of AFT2 (AFT2-1(up)), or overexpression of the wild-type AFT2 gene, led to partial complementation of the respiratory-deficient phenotype of the aft1Delta strain [1].
  • The kinetics of induction of two genes activated by the AFT2-1(up) allele are consistent with Aft2p acting as a direct transcriptional factor [1].
  • Aft2 is activated at a later time in Atm1-depleted cells [2].
  • Two transcriptional activators, Aft1 and Aft2, regulate iron homeostasis in Saccharomyces cerevisiae [2].

Biological context of AFT2

  • The yeast genome contains a paralog of AFT1, which has been designated AFT2 [1].
  • This study compares the functions of Aft1 and Aft2 in regulating the transcription of genes involved in iron homeostasis, with reference to the presence/absence of the paralog [3].
  • 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 [4].
  • Truncated forms of Aft1p and Aft2p bound to a DNA duplex containing the Aft1p binding site in vitro [1].
  • Although Aft1 and Aft2 sense a signal emanating from the Fe-S cluster biogenesis pathway, there is no indication that the proteins are inhibited by direct binding of an Fe-S cluster [2].

Other interactions of AFT2

  • Overproduction of Aft2p activates the transcription of the AFT1 target gene FET3 [4].
  • In addition, both proteins regulate MRS4 via a variant FeRE with Aft2p being the stronger activator from this particular element [5].
  • Thus, iron sensing by Aft1/Aft2 is not linked to the maturation of cytosolic/nuclear Fe-S proteins, but the mitochondrial inner membrane transporter Atm1 is important to transport the inhibitory signal [2].

Analytical, diagnostic and therapeutic context of AFT2


  1. A second iron-regulatory system in yeast independent of Aft1p. Rutherford, J.C., Jaron, S., Ray, E., Brown, P.O., Winge, D.R. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  2. Activation of the iron regulon by the yeast Aft1/Aft2 transcription factors depends on mitochondrial but not cytosolic iron-sulfur protein biogenesis. Rutherford, J.C., Ojeda, L., Balk, J., Mühlenhoff, U., Lill, R., Winge, D.R. J. Biol. Chem. (2005) [Pubmed]
  3. Direct activation of genes involved in intracellular iron use by the yeast iron-responsive transcription factor Aft2 without its paralog Aft1. Courel, M., Lallet, S., Camadro, J.M., Blaiseau, P.L. Mol. Cell. Biol. (2005) [Pubmed]
  4. Aft2p, a novel iron-regulated transcription activator that modulates, with Aft1p, intracellular iron use and resistance to oxidative stress in yeast. Blaiseau, P.L., Lesuisse, E., Camadro, J.M. J. Biol. Chem. (2001) [Pubmed]
  5. Aft1p and Aft2p mediate iron-responsive gene expression in yeast through related promoter elements. Rutherford, J.C., Jaron, S., Winge, D.R. J. Biol. Chem. (2003) [Pubmed]
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