Disease relevance of FRE2

• Two yeast genes, FRE1 and FRE2 (encoding Fe(III) reductases) were placed under the control of the cauliflower mosaic virus 35S promoter and introduced into tobacco (Nicotiana tabacum L.) via Agrobacterium tumefaciens-mediated transformation [1].

High impact information on FRE2

• We have shown that Nhp6 interacts directly with the Aft1 N-half, including the DNA-binding region, to facilitate Aft1 binding at FRE2 UAS [2].
• We found Nhp6a/b yeast HMG-box chromatin-associated architectural factors and Ssn6 (Cyc8) corepressor to be crucial transcriptional coactivators of FRE2 gene [2].
• This Nhp6/Ssn6 role in Aft1-mediated transcription is FRE2 promoter context specific, and both regulators are required for activation-dependent chromatin remodeling [2].
• Nhp6 facilitates Aft1 binding and Ssn6 recruitment, both essential for FRE2 transcriptional activation [2].
• FRE1 and FRE2 encode plasma membrane ferric reductases, obligatory for ferric iron assimilation, and FET3 encodes a copper-dependent membrane-associated oxidase required for ferrous iron uptake [3].

Biological context of FRE2

• The yeast genome contains five additional FRE1 and FRE2 homologues, four of which are regulated by iron and the major iron-dependent transcription factor, Aft1p, but whose function remains unknown [4].
• The Saccharomyces cerevisiae genome contains nine open reading frames (ORFs)--YLR214w (FRE1), YKL220c (FRE2), YOR381w, YNR060w, YOR384w, YLL051c, YOL152w, YGL160w and YLR047c--which, based on amino acid sequence similarity, fall in the category of iron/copper reductase-related genes [5].

Anatomical context of FRE2

• Reduction of iron (III) outside the cell is accomplished by means of reductases encoded by FRE1 and FRE2, homologues of the gp91-phox component of the oxygen reductase of human granulocytes [6].
• Fre1p and Fre2p are ferric reductases which account for the total plasma membrane associated activity, a prerequisite for iron uptake, in Saccharomyces cerevisiae [7].

Associations of FRE2 with chemical compounds

• FRE1 and FRE2 encode cell surface metalloreductases that are required for reduction and uptake of free ferric iron [4].
• The high affinity uptake systems for iron and copper ions in Saccharomyces cerevisiae involve metal-specific permeases and two known cell surface Cu(II) and Fe(III) metalloreductases, Fre1 and Fre2 [8].
• Cell-surface reductases, FRE1 and FRE2, provide ferrous iron for both systems [9].
• Elevated Fe(III) reduction was also observed in all FRE2 and some FRE1 lines [1].

Regulatory relationships of FRE2

• The yeast Fre1p/Fre2p cupric reductases facilitate copper uptake and are regulated by the copper-modulated Mac1p activator [7].

Other interactions of FRE2

• In contrast, cells that overexpressed FRE2 had maximal ferrireductase activity when NCP1 was repressed [10].
• Aft1 protein is required for maintaining detectable non-induced level of FET3 expression and for induction of FRE2 in iron starvation conditions [11].

Analytical, diagnostic and therapeutic context of FRE2

• Northern-blot analyses revealed mRNA of two different sizes in FRE1 lines, whereas all FRE2 lines had mRNA only of the expected length [1].

References