Reactome | Response to metal ions

Response to metal ions

Stable Identifier

R-HSA-5660526

DOI

10.3180/r-hsa-5660526.2

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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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, Günther 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
19021537	Mechanisms of mammalian zinc-regulated gene expression Jackson, KA, Coneyworth, LJ, Valentine, RA, Ford, D, Mathers, JC	Biochem. Soc. Trans.	2008
25405524	Balance between metallothionein and metal response element binding transcription factor 1 is mediated by zinc ions (review) Wang, Q, Dou, Y, Dong, G, Chen, H, Qi, M	Mol Med Rep	2015
17462582	Understanding the mechanisms of zinc-sensing by metal-response element binding transcription factor-1 (MTF-1) Andrews, GK, Laity, JH	Arch. Biochem. Biophys.	2007
22289350	The taste of heavy metals: gene regulation by MTF-1 Lindert, U, Günther, V, Schaffner, W	Biochim. Biophys. Acta	2012