Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Lysine-63-linked polyubiquitination: a principal target of cadmium carcinogenesis

  • Received : 2023.12.10
  • Accepted : 2024.03.27
  • Published : 2024.07.15
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Abstract

Cadmium is an environmental pollutant that constitutes a major danger to human health. It is considered a definite human carcinogen. The lung and kidney are the most sensitive organs for cancer development, and we recently provided the first evidence of direct upregulation of lysine-63-linked polyubiquitination by cadmium, particularly in response to environmentally relevant concentrations. Investigations of K63 polyubiquitination have greatly progressed, and various strategies have been reported for studying this molecular process in different biological systems under both physiological and stress conditions. Furthermore, the mechanisms underlying cadmium-induced accumulation of K63-polyubiquitinated proteins in lung and renal cells continue to be of interest given the unknown mechanism involved in the carcinogenesis of this metal. Cadmium is persistent within the cytosol and induces oxidative stress, which continuously damages proteins and causes K63 polyubiquitination, leading to the regulation/activation of different cellular signaling pathways. The aim of this review was to perform a critical analysis of the knowledge about K63 polyubiquitination induced by cadmium and its effect on selective autophagy, CYLD, the NF-KB pathway and Hif-1α. We also report data obtained in different experimental studies using cadmium, highlighting similarities in the induction of the ubiquitination system. A more detailed discussion will concern the role of K63 polyubiquitination in cadmium-exposed renal proximal convoluted tubules and lung cells since they are suitable model systems that are extremely sensitive to environmental stress, and cadmium is one of the most carcinogenic metals to which humans are exposed. We ultimately concluded that K63 polyubiquitination may be the origin of cadmium carcinogenesis in the lung and kidney.

Keywords

Acknowledgement

The author would like to extend their sincere appreciation to University of Jendouba Tunisia. The author would like to thank Baharia Mograbi and Helene Desqueyroux for helpful discussions, and the team AJE for proofreading and improving the clarity and readability of the English of our manuscript.

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