Physiological Functions of the Ubiquitin Ligases Nedd4-1 and Nedd4-2

Physiology (Bethesda). 2024 Jan 1;39(1):18-29. doi: 10.1152/physiol.00023.2023. Epub 2023 Nov 14.

Abstract

The Nedd4 family of E3 ubiquitin ligases, consisting of a C2-WW(n)-HECT domain architecture, includes the closely related Nedd4/Nedd4-1 and Nedd4L/Nedd4-2, which play critical roles in human physiology and pathophysiology.This review focuses on the regulation of enzymatic activity of these Nedd4 proteins, as well as on their roles in regulating stability and function of membrane and other signaling proteins, such as ion channels, ion transporters, and growth factor receptors. The diseases caused by impairment of such regulation are discussed, as well as opportunities and challenges for targeting these enzymes for therapy.

Keywords: E3 ubiquitin ligase; NEDD4L; Nedd4; signaling; ubiquitin.

Publication types

  • Review

MeSH terms

  • Endosomal Sorting Complexes Required for Transport* / genetics
  • Endosomal Sorting Complexes Required for Transport* / metabolism
  • Humans
  • Nedd4 Ubiquitin Protein Ligases / genetics
  • Nedd4 Ubiquitin Protein Ligases / metabolism
  • Ubiquitin* / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ubiquitination

Substances

  • Endosomal Sorting Complexes Required for Transport
  • Nedd4 Ubiquitin Protein Ligases
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Nedd4L protein, human
  • Nedd4 protein, human