Cullin3/KCTD5 induces monoubiquitination of ΔNp63α and impairs its activity

FEBS Lett. 2018 Jul;592(13):2334-2340. doi: 10.1002/1873-3468.13104. Epub 2018 Jun 1.

Abstract

Potassium channel tetramerization domain containing 5 (KCTD5) was previously documented as a component of the Cullin3-RING ligase (CRL3). It has been reported that KCTD5 can induce enrichment of polyubiquitinated proteins, and KCTD5-based CRL3 destabilizes several proteins. In our present study, we report that KCTD5 may physically interact with ΔNp63α, which is a member of the p53 family. Our further investigation revealed that Cullin3/KCTD5 can induce monoubiquitination of ΔNp63α. Cullin3/KCTD5 downregulates the DNA-binding affinity of ΔNp63α, impairing either its transactivity or its transinhibitory activity. Functionally, Cullin3/KCTD5 abates the proproliferation activity of ΔNp63α. These findings suggest that KCTD5-based CRL3 may mediate monoubiquitination and is a novel regulator of ΔNp63α.

Keywords: Cullin3; KCTD5; proproliferation; transactivity; ubiquitination; ΔNp63α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Cullin Proteins / physiology*
  • HEK293 Cells
  • Humans
  • Potassium Channels / metabolism
  • Potassium Channels / physiology*
  • Protein Binding
  • Protein Multimerization
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / metabolism*
  • Ubiquitin-Protein Ligases / physiology
  • Ubiquitination*

Substances

  • CUL3 protein, human
  • Cullin Proteins
  • KCTD5 protein, human
  • Potassium Channels
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Ubiquitin-Protein Ligases