Article

Nedd4 and Nedd4-2: closely related ubiquitin-protein ligases with distinct physiological functions

Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
Cell death and differentiation (Impact Factor: 8.39). 07/2009; 17(1):68-77. DOI: 10.1038/cdd.2009.84
Source: PubMed

ABSTRACT The Nedd4 (neural precursor cell-expressed developmentally downregulated gene 4) family of ubiquitin ligases (E3s) is characterized by a distinct modular domain architecture, with each member consisting of a C2 domain, 2-4 WW domains, and a HECT-type ligase domain. Of the nine mammalian members of this family, Nedd4 and its close relative, Nedd4-2, represent the ancestral ligases with strong similarity to the yeast, Rsp5. In Saccharomyces cerevisiae Rsp5 has a key role in regulating the trafficking, sorting, and degradation of a large number of proteins in multiple cellular compartments. However, in mammals the Nedd4 family members, including Nedd4 and Nedd4-2, appear to have distinct functions, thereby suggesting that these E3s target specific proteins for ubiquitylation. In this article we focus on the biology and emerging functions of Nedd4 and Nedd4-2, and review recent in vivo studies on these E3s.

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