Identification of F‐box proteins that are involved in resistance to methylmercury in <i>Saccharomyces cerevisiae</i>

Hwang, Gi-Wook; Ishida, Yasuhiro; Naganuma, Akira

doi:10.1016/j.febslet.2006.11.045

Cited by 27 publications

(26 citation statements)

References 27 publications

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“…Hrt3 (high-level expression reduces Ty3 transposition) and Ylr224w in S. cerevisiae both promote resistance to methylmercury, a highly toxic compound (75). Overproduction of these two F-box proteins elevated resistance to the toxic compound, in contrast to 15 other F-box proteins studied.…”

Section: Hrt3: An F-box Protein Enhancing Methylmercury Resistancementioning

confidence: 84%

Lessons from Fungal F-Box Proteins

Jonkers

Rep

2009

Eukaryot Cell

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Section: Hrt3: An F-box Protein Enhancing Methylmercury Resistancementioning

confidence: 84%

Lessons from Fungal F-Box Proteins

Jonkers

Rep

2009

Eukaryot Cell

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“…The empty vector pKT10 has been previously described (19). A TMC1 overexpression vector under the control of the GAPDH promoter was constructed by cloning the open reading frame of TMC1 into pKT10 to produce pGM1.…”

Section: Methodsmentioning

confidence: 99%

Tmc1 Is a Dynamically Regulated Effector of the Rpn4 Proteotoxic Stress Response

Guerra-Moreno

Hanna

2016

Journal of Biological Chemistry

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The ubiquitin-proteasome system represents the major pathway of selective intracellular protein degradation in eukaryotes. Misfolded proteins represent an important class of substrates for this pathway, and the failure to destroy misfolded proteins is associated with a number of human diseases. The transcription factor Rpn4 mediates a key proteotoxic stress response whose best known function is to control proteasome abundance by a homeostatic feedback mechanism. Here we identify the uncharacterized zinc finger protein Tmc1 as a dynamically regulated stress-responsive protein. Rpn4 induces TMC1 transcription in response to misfolded proteins. However, this response is counteracted by rapid proteasome-dependent degradation of Tmc1, which serves to normalize Tmc1 protein levels after induction. Precise control of Tmc1 levels is needed in vivo to survive multiple stressors related to proteostasis. Thus, Tmc1 represents a novel effector and substrate of the Rpn4 proteotoxic stress response.

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“…MeHg-induced changes in cellular Ca 2ϩ have been shown to be important (4)(5)(6)(7), as has oxidative stress (4), and glutamate metabolism (8). In both yeast and human cells, overexpression of the ubiquitin-targeting enzyme Cdc34 confers protection against the cytotoxic effects of MeHg, which leads to the suggestion that an unknown protein containing a signal for ubiquitination by Cdc34 is involved in the development of the cytotoxic effects of MeHg (9)(10)(11).…”

Section: T Oxic Organic Mercury Compounds Worry Many Communitiesmentioning

confidence: 99%

Localizing organomercury uptake and accumulation in zebrafish larvae at the tissue and cellular level

Korbas

Blechinger

Krone

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

124

112

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Using synchrotron x-ray fluorescence mapping, we have examined the uptake and localization of organic mercury in zebrafish larvae. Strikingly, the greatest accumulation of methyl and ethyl mercury compounds was highly localized in the rapidly dividing lens epithelium, with lower levels going to brain, optic nerve, and various other organs. The data suggest that the reported impairment of visual processes by mercury may arise not only from previously reported neurological effects, but also from direct effects on the ocular tissue. This novel approach is a powerful tool for directly investigating the molecular toxicology of heavy metals, and should be equally applicable to the study of a wide range of elements in developing embryos.methylmercury ͉ thimerosal ͉ x-ray fluorescence mapping ͉ eye lens T oxic organic mercury compounds worry many communities worldwide, yet the detailed mechanisms underlying their transport and toxicity remain uncertain (1). These neurotoxic compounds are particularly insidious due to the latency in onset of toxic symptoms and have caused several devastating masspoisonings of humans. Adults are affected, but exposure in utero has resulted in severe consequences such as microcephaly, cerebropalsy, seizures, and mental retardation. Methylmercury (MeHg) compounds are actively transported across cell membranes (2) although not, as originally thought, by molecular mimicry of methionine (3). Beyond this, however, our knowledge of the mechanisms underlying organic mercury (Hg) toxicity is fragmentary. MeHg-induced changes in cellular Ca 2ϩ have been shown to be important (4-7), as has oxidative stress (4), and glutamate metabolism (8). In both yeast and human cells, overexpression of the ubiquitin-targeting enzyme Cdc34 confers protection against the cytotoxic effects of MeHg, which leads to the suggestion that an unknown protein containing a signal for ubiquitination by Cdc34 is involved in the development of the cytotoxic effects of MeHg (9-11).Zebrafish (Danio rerio) are common model organisms for the study of embryonic development, and have found increasing use in vertebrate toxicology (12). While embryonic and larval zebrafish previously have been used to study the toxic effects of MeHg exposure at the whole body (13,14) and at the molecular level (15), there are no available data on MeHg uptake and accumulation with respect to different tissues and organs. Such information is critical to properly integrate information on tissue and cell specific impacts of Hg with uptake and accumulation of the metal at the whole animal level. We present herein a novel approach to the investigation of heavy-metal toxicity using synchrotron x-ray fluorescence imaging (16) to directly image metal localization within zebrafish larvae and to observe remarkable differential accumulation of organic Hg using this technique. Strikingly, we find that both methyl and ethyl Hg derivatives are concentrated to the greatest degree in lens epithelium with lower levels present in the brain, optic nerve, and other organs....

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Identification of F‐box proteins that are involved in resistance to methylmercury in Saccharomyces cerevisiae

Cited by 27 publications

References 27 publications

Lessons from Fungal F-Box Proteins

Lessons from Fungal F-Box Proteins

Tmc1 Is a Dynamically Regulated Effector of the Rpn4 Proteotoxic Stress Response

Localizing organomercury uptake and accumulation in zebrafish larvae at the tissue and cellular level

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