Eucaryotic metallothioneins: proteins, gene regulation and copper homeostasis
Moenne, A. (2001). Eucaryotic metallothioneins: proteins, gene regulation and copper homeostasis. Cah. Biol. Mar. 42(1-2): 125-135 In: Cahiers de Biologie Marine. Station Biologique de Roscoff: Paris. ISSN 0007-9723; e-ISSN 2262-3094, more Also appears in:(2001). Proceedings of the International Workshop "Current approaches in basic and applied phycology". Cahiers de Biologie Marine, 42(1-2). [S.n.]: [s.l.]. 1-185 pp., more |   |
| Abstract | Heavy metals such as copper, iron and zinc are essential for eucaryotic cell viability and they are required only in trace amounts. High concentrations of these metals are toxic for the cells and they trigger different molecular response mechanisms. One of the best studied of such responses involves the synthesis of metallothioneins (MTs) which are low molecular weight, cysteine-rich proteins that bind heavy metals by means of their cysteine residues. MTs have been purified from different eucaryotic cells and their structural and heavy metal binding properties have been determined. MT genes have been cloned from animal cells, fungi, plants and algae and their transcriptional activation by heavy metals has been characterized. The overexpression of MTs results in the accumulation of heavy metals in the cells. The best studied model for copper tolerance and homeostasis is the yeast Saccharomyces cerevisiae. In this fungus, high concentrations of copper activate transcription of the gene coding for CUP1 MT. This process involves the binding of ACE1 transcription factor to the promoter of cup-1 gene. ACE1 directly binds copper ions and undergoes a conformational change that allows its binding to the promoter region. On the other hand, copper starvation triggers the transcriptional activation of at least two copper transporter genes and a copper reductase gene. This activation involves the binding of MAC1 factor to the promoter region of these genes. MAC1 is stable in the absence of copper but is degraded when it binds copper ions via its carboxy terminal domain. Therefore, ACE1 and MAC1 are transcription factors which are able to sense intracellular concentrations of copper and they are crucial for copper homeostasis mechanisms. The above mentioned are probably not the only mechanisms involved in copper tolerance and homeostasis. Therefore, additional effort will be required to elucidate other complementary mechanisms involved in these processes. |
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