Resistance to cadmium mediated by ubiquitin-dependent proteolysis (original) (raw)
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- Published: 28 January 1993
Nature volume 361, pages 369–371 (1993)Cite this article
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Abstract
CADMIUM is a potent poison for living cells. In man, chronic exposure to low levels of cadmium results in damage to kidneys and has been linked to neoplastic disease and ageing, and acute exposure can cause damage to a variety of organs and tissues1. Cadmium reacts with thiol groups and can substitute for zinc in certain proteins2, but the reason for its toxicity in vivo remains uncertain. In eukaryotes, an important selective proteolysis pathway for the elimination of abnormal proteins that are generated under normal or stress conditions is ATP-dependent and mediated by the ubiquitin system3–5. Substrates of this pathway are first recognized by ubiquitin-conjugating enzymes5–7 (or auxiliary factors) which covalently attach ubiquitin, a small and highly conserved protein, to specific internal lysine residues of proteolytic substrates. Ubiquitinated substrates are then degraded by the proteasome, a multisubunit protease complex8–10. Here we show that expression of this ubiquitin-dependent proteolysis pathway in yeast is activated in response to cadmium exposure and that mutants deficient in specific ubiquitin-conjugating enzymes are hypersensitive to cadmium. Moreover, mutants in the proteasome are hypersensitive to cadmium, suggesting that cadmium resistance is mediated in part by degradation of abnormal proteins. This indicates that a major reason for cadmium toxicity may be cadmium-induced formation of abnormal proteins.
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- Stefan Jentsch: To whom correspondence should be addressed.
Authors and Affiliations
- Friedrich-Miescher-Laboratorium der Max-Planck-Gesellschaft, Spemannstrasse 37-39, 7400, Tubingen, Germany
Joern Jungmann, Hans-Albert Reins & Stefan Jentsch - Institut fur Pflanzenphysiologie, Universitat Bayreuth, Postfach 3008, 8580, Bayreuth, Germany
Christian Schobert
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- Joern Jungmann
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Jungmann, J., Reins, HA., Schobert, C. et al. Resistance to cadmium mediated by ubiquitin-dependent proteolysis.Nature 361, 369–371 (1993). https://doi.org/10.1038/361369a0
- Received: 10 September 1992
- Accepted: 24 November 1992
- Issue Date: 28 January 1993
- DOI: https://doi.org/10.1038/361369a0