Significance
Zinc is essential for animal life, and zinc levels are carefully regulated by homeostatic mechanisms. In the model organism Caenorhabditis elegans, the HIZR-1 nuclear receptor directly binds zinc and mediates high zinc homeostasis by regulating transcription. Cadmium is structurally similar to zinc but is a prevalent environmental toxin. Here, we explore how animals respond to these similar metals. The results suggest that cadmium hijacks the high zinc homeostasis response by directly binding and activating HIZR-1. This is an example of cadmium functioning as an activating ligand for a zinc-regulated protein in contrast to the prevailing model that cadmium binding causes protein dysfunction. These results elucidate the interplay between these two metals and reveal an unexpected mechanism of cadmium transcriptional control.
Abstract
Cadmium is an environmental pollutant and significant health hazard that is similar to the physiological metal zinc. In Caenorhabditis elegans, high zinc homeostasis is regulated by the high zinc activated nuclear receptor (HIZR-1) transcription factor. To define relationships between the responses to high zinc and cadmium, we analyzed transcription. Many genes were activated by both high zinc and cadmium, and hizr-1 was necessary for activation of a subset of these genes; in addition, many genes activated by cadmium did not require hizr-1, indicating there are at least two mechanisms of cadmium-regulated transcription. Cadmium...
Read Full Story: https://www.pnas.org/content/118/42/e2022649118
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