Regulation of the cadmium stress response through SCF-like ubiquitin ligases:: comparison between Saccharomyces cerevisiae, Schizosaccharomyces pombe and mammalian cells

Saccharomyces cerevisiae has developed several mechanisms to cope with exposure to cadmium. In particular, the sulfur compound glutathione plays a pivotal role in cadmium detoxification, and exposure to cadmium leads to a wide reorganization of S. cerevisiae transcriptome and proteome, resulting in a significant increase in glutathione synthesis. Met4, the transcriptional activator of the sulfur metabolism enzymes, is a critical actor in this reorganization. Recent work has uncovered a part of the mechanism of cadmium-induced Met4 regulation, and. showed that M,130 it occurs trough the SCIF ubiquitin ligase complex SCF. We discuss this regulation in S. cerevisiae and compare it with the regulation of two other transcriptional activators involved in cadmium detoxification: the Schizosaccharomyces pombe Zip1, regulated by SCFPof1, and the mammalian Nrf2, regulated by the SCF-like ubiquitin ligase Cul3:Rbx1:Keap1. (c) 2006 Elsevier Masson SAS. All rights reserved.