Biochemistry, Biophysics, and Structural Biology Commons^™

Cadmium-Mediated Rescue From Er-Associated Degradation Induces Expression Of Its Exporter, David J. Adle, Wenzhong Wel, Nathan Smith, Joshua J. Bles, Jaekwon Lee

Department of Biochemistry: Faculty Publications

Cadmium is a highly toxic environmental contaminant that has been implicated in various disorders. A major mechanism for cadmium detoxification in the yeast Saccharomyces cerevisiae relies on extrusion via Pca1, a P-type ATPase. While an N-terminal degron targets Pca1 for degradation before its secretion to the plasma membrane, cadmium in the growth media rapidly upregulates Pca1 by preventing its turnover. Here we show that the endoplasmic reticulum-associated degradation (ERAD) system, known for its role in quality control of secretory proteins, is unexpectedly responsible for the regulation of Pca1 expression by cadmium. Direct cadmium sensing at the ER by a degron …