Itch promotes the neddylation of JunB and regulates JunB-dependent transcription

Cell Signal. 2016 Sep;28(9):1186-1195. doi: 10.1016/j.cellsig.2016.05.016. Epub 2016 May 28.

Abstract

Protein neddylation is essential for the viability of most organisms and is widely involved in the regulation of immunity, DNA damage and repair, cell signaling and cell cycle. Unlike RING-type neddylation ligases, HECT-type neddylation ligase remains less defined. Here, we show that Itch is a novel HECT-type neddylation E3 ligase and we identify JunB as a substrate of Nedd8 modification by Itch. JunB neddylation attenuates its transcriptional activity. In addition, JunB neddylation mediated by Itch promotes its ubiquitination-dependent degradation. Therefore, these findings define a new HECT-type neddylation ligase and its neddylation substrate.

Keywords: Itch; JunB; Neddylation ligase; Transcriptional activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • HCT116 Cells
  • HEK293 Cells
  • Humans
  • NEDD8 Protein / metabolism*
  • Protein Binding
  • Proteolysis
  • Repressor Proteins / metabolism*
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Ubiquitin-Conjugating Enzymes / metabolism
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • JunB protein, human
  • NEDD8 Protein
  • Repressor Proteins
  • Transcription Factors
  • Ubiquitin-Conjugating Enzymes
  • ITCH protein, human
  • Ubiquitin-Protein Ligases
  • UBE2M protein, human