Predisposition to mouse thymic lymphomas in response to ionizing radiation depends on variant alleles encoding metal-responsive transcription factor-1 (Mtf-1)

Tamura, Yasushi; Maruyama, Masaki; Mishima, Yukio; Fujisawa, Hitoshi; Obata, Miki; Kodama, Yasumitsu; Yoshikai, Yoshihiro; Aoyagi, Yoshinobu; Niwa, Ohtsura; Schaffner, Walter; Kominami, Ryo

doi:10.1038/sj.onc.1208197

Cited by 26 publications

(19 citation statements)

References 39 publications

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“…Polymorphism in murine Mtf1 gene has been found to associate with the susceptibility to experimental g-ray-induced thymic lymphomas. This observation points at possible involvement of human MTF1 polymorphisms in the modulation of radiation-induced malignancies (Tamura et al 2005).…”

Section: Introductionmentioning

confidence: 66%

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Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma

Akulevich¹,

Saenko²,

Rogounovitch³

et al. 2009

Endocrine-Related Cancer

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121

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Papillary thyroid carcinoma (PTC) etiologically occurs as a radiation-induced or sporadic malignancy. Genetic factors contributing to the susceptibility to either form remain unknown. In this retrospective case-control study, we evaluated possible associations between singlenucleotide polymorphisms (SNPs) in the candidate DNA damage response genes (ATM, XRCC1, TP53, XRCC3, MTF1) and risk of radiation-induced and sporadic PTC. A total of 255 PTC cases (123 Chernobyl radiation-induced and 132 sporadic, all in Caucasians) and 596 healthy controls (198 residents of Chernobyl areas and 398 subjects without history of radiation exposure, all Caucasians) were genotyped. The risk of PTC and SNPs interactions with radiation exposure were assessed by logistic regressions. The ATM G5557A and XRCC1 Arg399Gln polymorphisms, regardless of radiation exposure, associated with a decreased risk of PTC according to the multiplicative and dominant models of inheritance (odds ratio (OR)Z0.69, 95% confidence interval (CI) 0.45-0.86 and ORZ0.70, 95% CI 0.59-0.93 respectively). The ATM IVS22-77 TOC and TP53 Arg72Pro SNPs interacted with radiation (PZ0.04 and PZ0.01 respectively). ATM IVS22-77 associated with the increased risk of sporadic PTC (ORZ1.84, 95% CI 1.10-3.24) whereas TP53 Arg72Pro correlated with the higher risk of radiogenic PTC (ORZ1.80, 95% CI 1.06-2.36). In the analyses of ATM/TP53 (rs1801516/rs664677/rs609429/rs1042522) combinations, the GG/TC/CG/GC genotype strongly associated with radiation-induced PTC (ORZ2.10, 95% CI 1.17-3.78). The GG/CC/GG/GG genotype displayed a significantly increased risk for sporadic PTC (ORZ3.32, 95% CI 1.57-6.99). The results indicate that polymorphisms of DNA damage response genes may be potential risk modifiers of ionizing radiation-induced or sporadic PTCs.

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Section: Introductionmentioning

confidence: 66%

“…MTF1 protein interacts with metallothioneins that are able to suppress cellular stresses generated by IR and other agents (Tamura et al 2005). Polymorphism in murine Mtf1 gene has been found to associate with the susceptibility to experimental g-ray-induced thymic lymphomas.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma

Akulevich¹,

Saenko²,

Rogounovitch³

et al. 2009

Endocrine-Related Cancer

Self Cite

121

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“…The target genes of MTF1 responsible to its function in liver and lymphocyte development remain elusive. In addition, linkage analysis and haplotype mapping identified Mtf1 as a lymphoma susceptibility gene in mice, because a mutation in MTF1 (S424P) predisposes mice to ionizing radiation-induced thymic lymphomas, presumably by up-regulating radiation-resistant genes to promote tumor growth (21). In mammalian cells, coordinated regulation of MTs and zinc transporter 1 by MTF1 plays a major role in protection against the toxicity of zinc and other metals (22).…”

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confidence: 99%

Induction of Metallothionein I by Arsenic via Metal-activated Transcription Factor 1

2009

Journal of Biological Chemistry

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Metal-activated transcription factor 1 (MTF1) mediates the induction of metallothioneins I and II by zinc and stress signals. The mechanism of MTF1 activation has not been well understood. We analyzed the interaction between arsenic (As 3؉ ) and MTF1 for Mt1 induction. As 3؉ potently induces Mt1 mRNA expression in mouse hepa1c1c7 cells. Induction is dependent upon functional MTF1 as induction is lost in Mtf1 knockout cells but is restored upon reconstitution with Mtf1; moreover, As 3؉ induces the binding of MTF1 to the metal response elements of endogenous Mt1. Induction is not affected by modulating zinc concentrations but is markedly enhanced by cycloheximide. Phenylarsine oxide (PAO), which covalently binds to vicinal protein cysteine thiol groups, induces Mt1 with a magnitude of higher potency than that of As 3؉ . PAO affinity beads effectively pulls down the carboxyl half of MTF1 (MTF1 321-675 ) by binding to a cluster of five cysteine residues near the terminus. Preincubation with As 3؉ , Cd 2؉ , Co 2؉ , Ni 2؉ , Ag ؉ , Hg 2؉ , and Bi 3؉ blocks pulldown of MTF1 321-675 by PAO beads in vitro and in vivo, indicating that binding of the metal inducers to the same C-terminal cysteine cluster as PAO occurs. Deletion of the C-terminal cysteine cluster or mutation of the cysteine residues abolishes or markedly reduces the transcription activation activity of MTF1 and the ability of MTF1 to restore Mt1 induction in Mtf1 knockout cells. The findings demonstrate a critical role of the C-terminal cysteine cluster of MTF1 in arsenic sensing and gene transcription via arsenic-cysteine thiol interaction.Humans are constantly exposed to a wide variety of metals from dietary, environmental, and occupational sources. Trace elements, such as copper, iron, and zinc, are required for certain biological functions under physiological concentrations. However, most metals are toxic and cause a wide range of pathological conditions, including cancer, toxicity, and chronic diseases in humans (1, 2). Induction of metallothioneins (MT I and II), 2 metal transporters, and antioxidative proteins represent a major means of metal detoxification in the body to maintain trace elements within a physiological range or to protect the body from the damage by metal overload. MTs are small, cysteine-rich, metal-binding proteins expressed in all eukaryotes and some prokaryotes. (3)(4)(5). MTs regulate metal homeostasis by sequestering metals in protein-bound forms, providing a zinc reserve, and serving as a scavenger to quench ROS and other free radicals. On the other hand, metal transporters export metals out of the cells, and antioxidant proteins/enzymes antagonize metalinduced oxidative stress.

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“…68) An MTF-1 polymorphism, that alters the amino acid at position 424 from a serine in susceptibility strains to a proline in resistant strains, correlates with the different susceptibility to γ-ray induced mouse thymic lymphoma. 69) The MTF-1 polymorphism affects the efficiency of the transcription activation. The proline type MTF-1 shows higher metal responsiveness than the serine type MTF-1.…”

Section: Future Implicationsmentioning

confidence: 99%

Mechanisms of Heavy Metal Sensing by Metal Response Element-binding Transcription Factor-1

Kimura

Itoh

Andrews

2009

JOURNAL OF HEALTH SCIENCE

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Heavy metal homeostasis and detoxification systems are often regulated by changes in gene transcription. In higher eukaryotes, metal response element (MRE)-binding transcription factor-1 (MTF-1) is the only known metal-sensing transcription factor and zinc is the only heavy metal which can reversibly and directly activate the DNA-binding activity of MTF-1, leading to its nuclear retention, promoter binding and induction or repression of transcription. Although, cadmium, copper and oxidative stresses can cause the activation of the DNA-binding activity of MTF-1 in vivo, they apparently do so, at least in part, by causing the redistribution of intracellular zinc. MTF-1-dependent metal-sensing transcription mechanisms are not fully understood but clearly involve zinc binding to its unique zinc finger domain. Recently, zinc has been shown to induce the formation of a co-activator complex containing MTF-1 and the histone acetyltransferase p300 which plays an essential role in the activation of mouse metallothionein-I (MT-I) gene transcription. In this review, we focus on current understanding of the mechanisms by which MTF-1 senses heavy metals and activates gene expression.

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Predisposition to mouse thymic lymphomas in response to ionizing radiation depends on variant alleles encoding metal-responsive transcription factor-1 (Mtf-1)

Cited by 26 publications

References 39 publications

Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma

Polymorphisms of DNA damage response genes in radiation-related and sporadic papillary thyroid carcinoma

Induction of Metallothionein I by Arsenic via Metal-activated Transcription Factor 1

Mechanisms of Heavy Metal Sensing by Metal Response Element-binding Transcription Factor-1

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