Metallothionein
DefinitionThis section has been translated automatically.
Class of very small (6 to 7 kDa), non-enzymatic proteins. In one MT molecule there are about 20 cysteines that bind zinc in two regions (so-called a and b clusters). These clusters enable the cell to react particularly quickly to toxins such as heavy metal ions. In addition, metallothionein functions, e.g. in the regulation of the metal metabolism as well as in other metal-dependent processes, such as gene regulation.
General informationThis section has been translated automatically.
- The overexpression of metallothionein can lead to a sequestration of zinc ions and thus to a functional inactivation of the p53 tumor suppressor gene. MT overexpression, independent of p53 expression, could represent an important step in carcinogenesis and tumor progression.
- Furthermore, metallothionein plays an important role in detoxification processes of heavy metals, including the inactivation of metal-containing chemotherapeutics.
- An increased MT expression compared to healthy epithelium is also found in basal cell carcinomas, and even more so in spinocellular carcinomas.
- The expression of MT is increased by proinflammatory cytokines.
- Metallothionein overexpression in the primary tumor seems to be a prognostic factor for progression and survival of melanoma patients.
Note(s)This section has been translated automatically.
Various heavy metals such as arsenic displace the zinc ion from its binding to metallothionein (zinc finger), thus leading to an inactivation of tumour suppressor proteins. Studies in MT-deficient mice showed that the release of nuclear zinc ions depends on the presence of the zinc storage protein metallothionein. Proinflammatory cytokines can lead to a temporary increase in nuclear zinc concentration via the interaction of synthesized NO and the nuclear translocation of MT. At the end of this signaling pathway, zinc can influence gene regulation in inflammatory reactions.
LiteratureThis section has been translated automatically.
- Borges PC et al (2007) Metallothionein immunlocalization in actinic skin nonmelanoma carcinomas. Appl Immunohistochem Mol Morphol 15: 165-169
- Weinlich G, Zelger B (2007) Metallothionein overexpression, a highly significant prognostic factor in thin melanoma. Histopathology 51:280-283
- Weinlich G, Topar G, Eisendle K, Fritsch PO, Zelger B (2007) Comparison of metallothionein-overexpression with sentinel lymph node biopsy as prognostic factors in melanoma. J Eur Acad Dermatol Venereol 21: 669-677