Interactions between hERG and Nedd4-2.A, confocal images show that Nedd4-2 overexpression reduces hERG expression. The expression of hERG and Nedd4-2-HA is demonstrated by showing their intensities in the lines across both Nedd4-2-HA-nonexpressing and Nedd4-2-HA-expressing cells. B, hERG interacts with endogenous Nedd4-2. Nedd4-2 was detected in proteins precipitated with an anti-hERG antibody from whole cell proteins extracted from hERG-HEK, but not from HEK cells (n = 5). C, Nedd4-2 enhances hERG ubiquitination. hERG was detected in proteins precipitated with an anti-Ub antibody from whole cell proteins extracted from hERG-HEK cells, but not from HEK cells. Compared with pcDNA3 transfection, Nedd4-2 overexpression increases the hERG-Ub interaction (n = 6).