Down-regulating destruction: phosphorylation regulates the E3 ubiquitin ligase Nedd4-2.
E3 ubiquitin ligases catalyze ubiquitination, which can target specific proteins for degradation. Although a growing number of E3 ubiquitin ligases and their targets have been identified, much less is known about the mechanisms that regulate their activity. A convergence of data indicate that phosphorylation regulates the binding of Nedd4-2, a HECT (homologous to the E6-AP C terminus) domain E3 ubiquitin ligase, to its target, the epithelial Na(+) channel ENaC. Nedd4-2 phosphorylation is emerging as a central convergence point for the regulation of epithelial Na(+) transport.
Snyder
Peter M
PM
Department of Internal Medicine and Molecular Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA. petersnyder@uiowa.edu
D015536:Down-Regulation; D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels / Q000378:metabolism; D006801:Humans; D000075702:Nedd4 Ubiquitin Protein Ligases; D010766:Phosphorylation; D011506:Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
D056827:Endosomal Sorting Complexes Required for Transport; D053503:Epithelial Sodium Channels; D011506:Proteins; D000075702:Nedd4 Ubiquitin Protein Ligases; C000618483:Nedd4 protein, human; C000618485:Nedd4L protein, human; D044767:Ubiquitin-Protein Ligases