CaIPF7817 is involved in the regulation of redox homeostasis in Candida albicans

Jia, Jianhui; Wang, Yan; Cao, Yongbing; Gao, Ping-Hui; Jia, Xin‐Ming; Ma, Zhiliang; Xu, Ye; Dai, Bao-Di; Jiang, Yuanying

doi:10.1016/j.bbrc.2007.05.081

Cited by 11 publications

(9 citation statements)

References 29 publications

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“…IPF7817 is a member of the NAD(P)H oxidoreductase family that is strongly induced during oxidative stress [36,37]. It is supposed to be involved in the regulation of intracellular redox homeostasis, as mutants in which the gene was inactivated had increased intracellular levels of reactive oxygen species (ROS) and, presumably as a compensatory mechanism, upregulated other redox-related genes [38]. IPF17186 is a member of the ThiJ/PfpI protein family [39].…”

Section: Discussionmentioning

confidence: 99%

The Transcription Factor Mrr1p Controls Expression of the MDR1 Efflux Pump and Mediates Multidrug Resistance in Candida albicans

et al. 2007

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Constitutive overexpression of the MDR1 (multidrug resistance) gene, which encodes a multidrug efflux pump of the major facilitator superfamily, is a frequent cause of resistance to fluconazole and other toxic compounds in clinical Candida albicans strains, but the mechanism of MDR1 upregulation has not been resolved. By genome-wide gene expression analysis we have identified a zinc cluster transcription factor, designated as MRR1 (multidrug resistance regulator), that was coordinately upregulated with MDR1 in drug-resistant, clinical C. albicans isolates. Inactivation of MRR1 in two such drug-resistant isolates abolished both MDR1 expression and multidrug resistance. Sequence analysis of the MRR1 alleles of two matched drug-sensitive and drug-resistant C. albicans isolate pairs showed that the resistant isolates had become homozygous for MRR1 alleles that contained single nucleotide substitutions, resulting in a P683S exchange in one isolate and a G997V substitution in the other isolate. Introduction of these mutated alleles into a drug-susceptible C. albicans strain resulted in constitutive MDR1 overexpression and multidrug resistance. By comparing the transcriptional profiles of drug-resistant C. albicans isolates and mrr1Δ mutants derived from them and of C. albicans strains carrying wild-type and mutated MRR1 alleles, we defined the target genes that are controlled by Mrr1p. Many of the Mrr1p target genes encode oxidoreductases, whose upregulation in fluconazole-resistant isolates may help to prevent cell damage resulting from the generation of toxic molecules in the presence of fluconazole and thereby contribute to drug resistance. The identification of MRR1 as the central regulator of the MDR1 efflux pump and the elucidation of the mutations that have occurred in fluconazole-resistant, clinical C. albicans isolates and result in constitutive activity of this trancription factor provide detailed insights into the molecular basis of multidrug resistance in this important human fungal pathogen.

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Section: Discussionmentioning

confidence: 99%

The Transcription Factor Mrr1p Controls Expression of the MDR1 Efflux Pump and Mediates Multidrug Resistance in Candida albicans

et al. 2007

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“…Similarly, Oye32p is a putative NAD(P)H oxidoreductase, whose expression is also induced during oxidative stress [33, 34]. Mutants lacking this gene display increased levels of ROS compared to the wild-type strain; therefore, this enzyme may be involved in intracellular redox homeostasis in C. albicans [35]. …”

Section: Discussionmentioning

confidence: 99%

Proteomic analysis of Mrr1p‐ and Tac1p‐associated differential protein expression in azole‐resistant clinical isolates of Candida albicans

Hoehamer

Cummings

Hilliard

et al. 2009

Proteomics Clinical Apps

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Azole resistance in Candida albicans is frequently caused by the overexpression of multi-drug efflux pump genes MDR1, CDR1, and CDR2 due to gain-of-function mutations in the zinc cluster transcription factors Mrr1p and Tac1p. In this study, we performed a comparative proteomic analysis to identify proteins whose expression level is influenced by these transcription factors. Both 2-DE and PMF were used to examine the expression profiles of six pairs of matched C. albicans isolates carrying gain-of-function mutations in either MRR1 or TAC1 resulting in the overexpression of either MDR1 or CDR1 and CDR2. Using this approach, 17 differentially expressed proteins were identified in the MDR1-overexpressing isolates, while 14 were identified in the isolates that overexpress CDR1 and CDR2. Furthermore, we found that the expression of many of these proteins was increased in a wild-type strain of C. albicans after the introduction of a gain-of-function allele of MRR1 or TAC1. Moreover, disruption of MRR1 and TAC1 in isolates carrying gain-of-function mutations resulted in decreased expression of these proteins, confirming their regulation by Mrr1p or Tac1p. Several proteins involved in heat shock and carbohydrate metabolism were differentially expressed in all clinical isolate sets, but these proteins were not dependent upon either Tac1p or Mrr1p.

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“…42, 43, 44 The GSH content was determined using GSH and GSSG Assay Kit (S0053, Beyotime) as previously described. 45 The H 2 O 2 content was determined using a H 2 O 2 Assay Kit (S0038, Beyotime) as previously described. 46 …”

Section: Methodsmentioning

confidence: 99%

Cancer-derived immunoglobulin G promotes tumor cell growth and proliferation through inducing production of reactive oxygen species

et al. 2013

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Cancer cells have been found to express immunoglobulin G (IgG), but the exact functions and underlying mechanisms of cancer-derived IgG remain elusive. In this study, we first confirmed that downregulation of IgG restrained the growth and proliferation of cancer cells in vitro and in vivo. To elucidate its mechanism, we carried out a co-immunoprecipitation assay in HeLa cells and identified 27 potential IgG-interacting proteins. Among them, receptor of activated protein kinase C 1 (RACK1), ras-related nuclear protein (RAN) and peroxiredoxin 1 (PRDX1) are closely related to cell growth and oxidative stress, which prompted us to investigate the mechanism of action of IgG in the above phenomena. Upon confirmation of the interactions between IgG and the three proteins, further experiments revealed that downregulation of cancer-derived IgG lowered levels of intracellular reactive oxygen species (ROS) by enhancing cellular total antioxidant capacity. In addition, a few ROS scavengers, including catalase (CAT), dimethylsulfoxide (DMSO), n-acetylcysteine (NAC) and superoxide dismutase (SOD), further inhibited the growth of IgG-deficient cancer cells through suppressing mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK) signaling pathway induced by a low level of intracellular ROS, whereas exogenous hydrogen peroxide (H2O2) at low concentration promoted their survival via increasing intracellular ROS levels. Similar results were obtained in an animal model and human tissues. Taken together, our results demonstrate that cancer-derived IgG can enhance the growth and proliferation of cancer cells via inducing the production of ROS at low level. These findings provide new clues for understanding tumor proliferation and designing cancer therapy.

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CaIPF7817 is involved in the regulation of redox homeostasis in Candida albicans

Cited by 11 publications

References 29 publications

The Transcription Factor Mrr1p Controls Expression of the MDR1 Efflux Pump and Mediates Multidrug Resistance in Candida albicans

The Transcription Factor Mrr1p Controls Expression of the MDR1 Efflux Pump and Mediates Multidrug Resistance in Candida albicans

Proteomic analysis of Mrr1p‐ and Tac1p‐associated differential protein expression in azole‐resistant clinical isolates of Candida albicans

Cancer-derived immunoglobulin G promotes tumor cell growth and proliferation through inducing production of reactive oxygen species

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