Response to metal ions

Stable Identifier
R-HSA-5660526
Type
Pathway
Species
Homo sapiens
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Summation

Though metals such as zinc, copper, and iron are required as cofactors for cellular enzymes they can also catalyze damaging metal substitution or unspecific redox reactions if they are not sequestered. The transcription factor MTF1 directs the major cellular response to zinc, cadmium, and copper. MTF1 activates gene expression to up-regulate genes encoding proteins, such as metallothioneins and glutamate-cysteine ligase (GCLC), involved in sequestering metals. MTF1 represses gene expression to down-regulate genes encoding transporters that import the metals into the cell (reviewed in Laity and Andrews 2007, Jackson et al. 2008, GŁnther et al. 2012, Dong et al. 2015). During activation MTF1 in the cytosol binds zinc ions and is translocated into the nucleus, where it binds metal response elements in the promoters of target genes. Activation of MTF1 by cadmium and copper appears to be indirect as these metals displace zinc from metallothioneins and the displaced zinc then binds MTF1.
Metallothioneins bind metals and participate in detoxifying heavy metals, storing and transporting zinc, and redox biochemistry.

Literature References
PubMed ID Title Journal Year
25405524 Balance between metallothionein and metal response element binding transcription factor 1 is mediated by zinc ions (review)

Dong, G, Chen, H, Qi, M, Dou, Y, Wang, Q

Mol Med Rep 2015
19021537 Mechanisms of mammalian zinc-regulated gene expression

Jackson, KA, Valentine, RA, Coneyworth, LJ, Mathers, JC, Ford, D

Biochem. Soc. Trans. 2008
17462582 Understanding the mechanisms of zinc-sensing by metal-response element binding transcription factor-1 (MTF-1)

Laity, JH, Andrews, GK

Arch. Biochem. Biophys. 2007
22289350 The taste of heavy metals: gene regulation by MTF-1

GŁnther, V, Lindert, U, Schaffner, W

Biochim. Biophys. Acta 2012
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