Copper activates metallothionein gene transcription by altering the conformation of a specific DNA binding protein

Fürst, Peter; Hu, Shi Xue; Hackett, R H; Hamer, Dean H.

doi:10.1016/0092-8674(88)90229-2

Cited by 364 publications

(281 citation statements)

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“…It is now known that a ^raw^-acting regulatory protein, encoded by the ACE 1 locus (Thiele, 1988;Furstetal, 1988) and also known as the CUP2 locus Buchman et al, 1989), activates transcription of the Cu-MT gene in response to excess copper (or silver) ions . Although the ACEl gene is constitutively expressed in the absence or presence of copper, the apoprotein cannot bind DNA (Fiirst et al, 1988). However, in the presence of Cu(i) [or Ag(i)], the amino-terminal portion of the ACEl protein (amino acids 1-122) undergoes a conformational change which allows the protein specifically to bind to the CUPl upstream activator sequence (UAS) (Furst et al, 1988;Huibregtse, Enkelke & Thiele, 1989).…”

Section: Intracellular Fate Of Toxic Metals* (A) Metal-binding Proteimentioning

confidence: 99%

Interactions of fungi with toxic metals

1993

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SUMMARY This review details the major interactions of fungi with toxic metal species. Physico‐chemical and biological aspects are discussed including definitions and classification of metals in biological contexts, mechanisms of metal fungitoxicity, resistance and tolerance, environmental influences and the occurrence of fungi in metal‐polluted habitats. Cellular interactions include extracellular precipitation and complexation, binding to cell walls, transport of monovalent and divalent metal cations, intracellular fates of toxic metal species (including metal‐binding proteins and peptides, and vacuolar compartmentation), and metal transformations including organometal(loid) synthesis. Significant interactions between metals and mycorrhizal fungi and macrofungi are summarized with reference to the amelioration of plant phytotoxicity and metal accumulation respectively. Biotechnological aspects of metal‐fungal interactions relate to the biological treatment of metal‐contaminated effluents and waste streams for metal removal/recovery and environmental protection.

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Section: Intracellular Fate Of Toxic Metals* (A) Metal-binding Proteimentioning

confidence: 99%

Interactions of fungi with toxic metals

1993

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“…MTF-1 is a zinc-dependent, zinc-responsive transcription factor (Westin and Schaffner, 1988;Heuchel et al, 1994). In yeast, for example, it has been demonstrated that the copper MT gene is induced through a copper-responsive element, and this process is mediated by the copper-binding transcription factor ACEl (Fü rst et al, 1988). ACE1 binds to a MRE upstream promoter of the target gene.…”

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Characterization of a Novel Plant Promoter Specifically Induced by Heavy Metal and Identification of the Promoter Regions Conferring Heavy Metal Responsiveness

Zhang

Chai

2006

Plant Physiology

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The bean (Phaseolus vulgaris) stress-related gene number 2 (PvSR2) gene responds to heavy metals but not to other forms of environmental stresses. To elucidate its heavy metal-regulatory mechanism at the transcriptional level, we isolated and characterized the promoter region (21623/148) of PvSR2. Deletions from the 5# end revealed that a sequence between 2222 and 2147 relative to the transcriptional start site was sufficient for heavy metal-specific induction of the promoter region of PvSR2. Detailed analysis of this 76-bp fragment indicated that heavy metal-responsive elements were localized in two regions (2222/2188 and 2187/2147), each of which could separately confer heavy metal-responsive expression on the b-glucuronidase gene in the context of a minimal cauliflower mosaic virus 35S promoter. Region I (2222/2188) contains a motif (metalregulatory element-like sequence) similar to the consensus metal-regulatory element of the animal metallothionein gene, and mutation of this motif eliminated the heavy metal-inducible function of region I. Region II (2187/2147) had no similarity to previously identified cis-acting elements involved in heavy metal induction, suggesting the presence of a novel heavy metalresponsive element. Transformed tobacco (Nicotiana tabacum) seedlings expressing b-glucuronidase under control of the PvSR2 promoter region (2687/148) showed heavy metal-specific responsive activity that depended on the type and concentration of the heavy metal and the type of organ. These findings further our understanding of the regulation of PvSR2 expression and provide a new heavy-metal-inducible promoter system in transgenic plants.In plants, a number of heavy metals are essential for normal growth as cofactors and as structural and catalytic components of proteins and enzymes. These micronutrients, as well as nonessential heavy metals such as cadmium, are toxic at high levels. Plants have evolved a suite of mechanisms that control and respond to the uptake and accumulation of both essential and nonessential heavy metals. These mechanisms include the chelation and sequestration of heavy metals by particular ligands including small peptides, organic acids, and amino acids, which bind free metal ions. They contribute to metal detoxification by buffering cytosolic metal ions (Clemens, 2001). The two best-characterized heavy metal-binding ligands in plant cells are the phytochelatins (PCs) and metallothioneins (MTs; for review, see Cobbett and Goldsborough, 2002). MTs are Cys-rich polypeptides encoded by a family of genes. In contrast, PCs are a family of enzymatically synthesized Cys-rich peptides. The induction of PC synthesis is based on the posttranscriptional activation of preformed PC synthase and is not under transcriptional control.Several heavy metal-inducible genes have been reported in plants (Hagen et al., 1988;Lescure et al., 1991;Berna and Bernier, 1999), but surprisingly, little is known about the transcriptional regulation of gene expression in response to heavy metals. In particular, the cis-...

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“…Ace1p cooperatively binds Cu(I) to form a tetra-Cu cluster through specific cysteine residues within the amino-terminal DNA binding domain (13,40). Copper binding leads to a conformational change in this domain that results in specific binding of monomeric Ace1p to the metal response elements (MREs) 5Ј-TCY (4)(5)(6) GCTG-3Ј (Y ϭ pyrimidine) on the promoters of genes that are involved in Cu ion detoxification and protection against oxidative damage (53).…”

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Dynamic Regulation of Copper Uptake and Detoxification Genes in Saccharomyces cerevisiae

Peña

Koch

Thiele

1998

Molecular and Cellular Biology

170

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The essential yet toxic nature of copper demands tight regulation of the copper homeostatic machinery to ensure that sufficient copper is present in the cell to drive essential biochemical processes yet prevent the accumulation to toxic levels. In Saccharomyces cerevisiae, the nutritional copper sensor Mac1p regulates the copper-dependent expression of the high affinity Cu(I) uptake genes CTR1, CTR3, and FRE1, while the toxic copper sensor Ace1p regulates the transcriptional activation of the detoxification genes CUP1, CRS5, and SOD1 in response to copper. In this study, we characterized the tandem regulation of the copper uptake and detoxification pathways in response to the chronic presence of elevated concentrations of copper ions in the growth medium. Upon addition of CuSO 4 , mRNA levels of CTR3 were rapidly reduced to eightfold the original basal level whereas the Ace1p-mediated transcriptional activation of CUP1 was rapid and potent but transient.

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Copper activates metallothionein gene transcription by altering the conformation of a specific DNA binding protein

Cited by 364 publications

References 45 publications

Interactions of fungi with toxic metals

Interactions of fungi with toxic metals

Characterization of a Novel Plant Promoter Specifically Induced by Heavy Metal and Identification of the Promoter Regions Conferring Heavy Metal Responsiveness

Dynamic Regulation of Copper Uptake and Detoxification Genes in Saccharomyces cerevisiae

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