A Copper-responsive Transcription Factor, CRF1, Mediates Copper and Cadmium Resistance in Yarrowia lipolytica

García, Sara Mallén; Prado, Marciano; Dégano, Rosa Ma; Domínguez, Ángel

doi:10.1074/jbc.m201091200

Cited by 48 publications

(31 citation statements)

References 43 publications

(55 reference statements)

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“…Functional orthologs of Ace1 confer copper resistance in Candida glabrata (Amt1) and Yarrowia lipolytica (Crf1) (46,173). Although Amt1 protects cells from copper by regulating the expression of three metallothionein genes, metallothionein expression is still copper responsive in a crf1 mutant strain (46,141,172). This latter result suggests that Crf1 guards against copper overload by regulating the expression of a yet-unidentified target gene(s) (46).…”

Section: Coppermentioning

confidence: 73%

“…Ace1 also regulates the expression of a second metallothionein gene (CRS5) and the copper and zinc superoxide dismutase gene (SOD1) (29,55). Functional orthologs of Ace1 confer copper resistance in Candida glabrata (Amt1) and Yarrowia lipolytica (Crf1) (46,173). Although Amt1 protects cells from copper by regulating the expression of three metallothionein genes, metallothionein expression is still copper responsive in a crf1 mutant strain (46,141,172).…”

Section: Coppermentioning

confidence: 99%

“…Amt1 autoregulates its own expression, a critical factor in copper resistance, since cells that are unable to autoactivate AMT1 are sensitive to growth on copper (174). Crf1 activity is subject to copper-dependent nuclear translocation (46).…”

Section: Coppermentioning

confidence: 99%

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Metal-Responsive Transcription Factors That Regulate Iron, Zinc, and Copper Homeostasis in Eukaryotic Cells

2004

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Iron, copper, and zinc are all essential nutrients. The electron transfer properties of iron and copper are fundamental to processes such as respiration and photosynthesis. Zinc forms the catalytic center in numerous enzymes and has an important structural role in a wide range of proteins. However, all these metals can be toxic if their levels and distribution are not carefully regulated, as their inappropriate binding may compromise cellular function. The uncontrolled redox activity of iron and copper can also lead to the generation of damaging oxygen radicals. Therefore, organisms maintain cytoplasmic metal concentrations at a nontoxic level that is sufficient for growth. A variety of homeostatic mechanisms have been identified, which include the control of translation and RNA stability by iron-regulatory proteins and the metal-dependent trafficking or degradation of metal transporters (39,109,138). This review focuses on the role that metal-responsive transcription factors have in regulating trace metal metabolism. These factors are able to sense changes in metal concentrations and coordinate the expression of genes that are involved in the acquisition, distribution, sequestration, and use of metals. Consequently, the ability to mediate metal-responsive gene expression is an important aspect of metal homeostasis in those organisms that contain these factors.

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Section: Coppermentioning

confidence: 73%

Section: Coppermentioning

confidence: 99%

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Metal-Responsive Transcription Factors That Regulate Iron, Zinc, and Copper Homeostasis in Eukaryotic Cells

2004

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“…3a; Altschul et al, 1997). This motif is found in several copper-responsive transcription factors, including Mac1p and Ace1p of S. cerevisiae (Jungmann et al, 1993;Szczypka & Thiele, 1989), Amt1p of Candida glabrata (Zhou & Thiele, 1991), Cuf1p of Schizosaccharomyces pombe (Labbe et al, 1999) and Crf1p of Yarrowia lipolytica (Garcia et al, 2002). In each corresponding organism, the motif facilitates the binding of protein to DNA in the presence of copper or silver (Furst & Hamer, 1989;.…”

Section: Resultsmentioning

confidence: 99%

The CaCTR1 gene is required for high-affinity iron uptake and is transcriptionally controlled by a copper-sensing transactivator encoded by CaMAC1

Marvin

Cashmore

2004

Microbiology

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The ability of Candida albicans to acquire iron from the hostile environment of the host is known to be necessary for virulence and appears to be achieved using a similar system to that described for Saccharomyces cerevisiae. In S. cerevisiae, high-affinity iron uptake is dependent upon the acquisition of copper. The authors have previously identified a C. albicans gene (CaCTR1) that encodes a copper transporter. Deletion of this gene results in a mutant strain that grows predominantly as pseudohyphae and displays aberrant morphology in low-copper conditions. This paper demonstrates that invasive growth by C. albicans is induced by low-copper conditions and that this is augmented in a Cactr1-null strain. It also shows that deletion of CaCTR1 results in defective iron uptake. In S. cerevisiae, genes that facilitate high-affinity copper uptake are controlled by a copper-sensing transactivator, ScMac1p. The authors have now identified a C. albicans gene (CaMAC1) that encodes a copper-sensing transactivator. A Camac1-null mutant displays phenotypes similar to those of a Cactr1-null mutant and has no detectable CaCTR1 transcripts in low-copper conditions. It is proposed that high-affinity copper uptake by C. albicans is necessary for reductive iron uptake and is transcriptionally controlled by CaMac1p in a similar manner to that in S. cerevisiae.

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“…The two oxidation states of copper (Cu + and Cu 2+ ) and its relatively broad redox potential when bound to protein (200-800 mV) make it important to metalloenzymes in many redox-driven reactions (Solioz & Stoyanov, 2003). While trace amounts of copper are essential for life, copper also catalyses the synthesis of reactive oxygen species, leading to severe damage of cytoplasmic constituents through the oxidation of proteins, cleavage of DNA and RNA, and lipid peroxidation (Garcia et al, 2002;Halliwell & Gutteridge, 1984). Copper also binds with high affinity to histidine, cysteine and methionine, resulting in the inactivation of proteins (Camakaris et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Molecular insight into extreme copper resistance in the extremophilic archaeon ‘Ferroplasma acidarmanus’ Fer1

et al. 2005

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‘Ferroplasma acidarmanus’ strain Fer1 is an extremely acidophilic archaeon involved in the genesis of acid mine drainage, and was isolated from copper-contaminated mine solutions at Iron Mountain, CA, USA. Here, the initial proteomic and molecular investigation of Cu2+ resistance in this archaeon is presented. Analysis of Cu2+ toxicity via batch growth experiments and inhibition of oxygen uptake in the presence of ferrous iron demonstrated that Fer1 can grow and respire in the presence of 20 g Cu2+ l−1. The Fer1 copper resistance (cop) loci [originally detected by Ettema, T. J. G., Huynen, M. A., de Vos, W. M. & van der Oost, J. Trends Biochem Sci 28, 170–173 (2003)] include genes encoding a putative transcriptional regulator (copY), a putative metal-binding chaperone (copZ) and a putative copper-transporting P-type ATPase (copB). Transcription analyses demonstrated that copZ and copB are co-transcribed, and transcript levels were increased significantly in response to exposure to high levels of Cu2+, suggesting that the transport system is operating for copper efflux. Proteomic analysis of Fer1 cells exposed to Cu2+ revealed the induction of stress proteins associated with protein folding and DNA repair (including RadA, thermosome and DnaK homologues), suggesting that ‘Ferroplasma acidarmanus’ Fer1 uses multiple mechanisms for resistance to high levels of copper.

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A Copper-responsive Transcription Factor, CRF1, Mediates Copper and Cadmium Resistance in Yarrowia lipolytica

Cited by 48 publications

References 43 publications

Metal-Responsive Transcription Factors That Regulate Iron, Zinc, and Copper Homeostasis in Eukaryotic Cells

Metal-Responsive Transcription Factors That Regulate Iron, Zinc, and Copper Homeostasis in Eukaryotic Cells

The CaCTR1 gene is required for high-affinity iron uptake and is transcriptionally controlled by a copper-sensing transactivator encoded by CaMAC1

Molecular insight into extreme copper resistance in the extremophilic archaeon ‘Ferroplasma acidarmanus’ Fer1

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