Cover photograph (Copyright © 2008, American Society for Microbiology. All Rights Reserved.): View of a cancer cell, represented as a machine shop, outlining novel posttranslational regulation of hERG1 K⁺ channel surface expression. Cancer cells highly express hERG1 isoforms containing the USO exon. These isoforms (blue cylinders) are retained in the endoplasmic reticulum (ER) (the tube resembling an assembly line); during the synthetic process, full-length hERG1 isoforms are also present in the ER (red cylinders). When a full-length hERG1 isoform come up against the hERG1 isoforms containing the USO exon, the former are retained in the ER and undergo ubiquitin-dependent degradation (hatchets emerging from blue cylinders). When a large amount of hERG1 isoforms containing the USO exon is present inside the cell, the trafficking of full-length hERG1 isoforms (green cylinders inside the cell) is impaired (hatchets cutting some of the green cylinders). On the whole, this process results in decreased hERG1 channel density on the plasma membrane (green cylinders on the cell surface) of cancer cells. (Image courtesy of Chiara Casazza.) (See related article on page 5043.)