Diverse and pivotal roles of neddylation in metabolism and immunity

FEBS J. 2021 Jul;288(13):3884-3912. doi: 10.1111/febs.15584. Epub 2020 Oct 20.

Abstract

Neddylation is one type of protein post-translational modification by conjugating a ubiquitin-like protein neural precursor cell-expressed developmentally downregulated protein 8 to substrate proteins via a cascade involving E1, E2, and E3 enzymes. The best-characterized substrates of neddylation are cullins, essential components of cullin-RING E3 ubiquitin-ligase complexes. The discovery of noncullin neddylation targets indicates that neddylation may have diverse biological functions. Indeed, neddylation has been implicated in various cellular processes including cell cycle progression, metabolism, immunity, and tumorigenesis. Here, we summarized the reported neddylation substrates and also discuss the functions of neddylation in the immune system and metabolism.

Keywords: MLN4924; immunity; metabolism; neddylation; substrate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle / physiology
  • Cullin Proteins / metabolism*
  • Energy Metabolism / physiology
  • Humans
  • Immunity / physiology
  • NEDD8 Protein / metabolism*
  • Protein Processing, Post-Translational / physiology*
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitins / metabolism*

Substances

  • Cullin Proteins
  • NEDD8 Protein
  • Ubiquitins
  • Ubiquitin-Protein Ligases