Sumoylation and ubiquitylation crosstalk in the control of ΔNp63α protein stability

Gene. 2018 Mar 1:645:34-40. doi: 10.1016/j.gene.2017.12.018. Epub 2017 Dec 12.

Abstract

ΔNp63α is finely and strictly regulated during embryogenesis and differentiation. ΔNp63α is the only p63 isoform degraded by the proteasome after Ubiquitin and SUMO (Small Ubiquitin-like MOdifier) conjugation. Here, we show that p63 ubiquitylation per se is not the signal triggering p63 proteasomal degradation. Taking advantage of natural ΔNp63α mutants isolated by patients with Split Hand and Foot Malformation IV syndrome, we found that SUMO and Ub modifications are not redundant and both are required to guarantee efficient ΔNp63α degradation. Here, we present evidence that sumoylation and ubiquitylation of ΔNp63α are strongly intertwined, and none of the two can efficiently occur if the other is impaired.

Keywords: Differentiation; GAM1; SFHM-IV syndrome; SUMO; Ubc9; p14ARF.

MeSH terms

  • Cell Line
  • HEK293 Cells
  • Humans
  • Limb Deformities, Congenital / genetics
  • Molecular Weight
  • Mutation
  • Proteasome Endopeptidase Complex / chemistry
  • Proteasome Endopeptidase Complex / metabolism
  • Protein Stability
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Sumoylation
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / chemistry*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Ubiquitin / metabolism
  • Ubiquitination

Substances

  • Small Ubiquitin-Related Modifier Proteins
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Ubiquitin
  • Proteasome Endopeptidase Complex