PKCδ stabilizes TAp63 to promote cell apoptosis

FEBS Lett. 2015 Jul 22;589(16):2094-9. doi: 10.1016/j.febslet.2015.06.014. Epub 2015 Jun 23.

Abstract

PKCδ and p63 are respectively reported to play important roles in cell apoptosis. But there is no report on interaction between them in regulation of apoptosis. In the present study, we found that PKCδ can directly associate and up-regulate TA isoforms of p63 (TAp63) proteins via increasing their stability. PKCδ kinase activity and Thr157 site in TAp63 are crucial for this PKCδ-induced accumulation of TAp63. PKCδ can also enhance TAp63-mediated transcription and cell apoptosis. Taken together, our data indicate that PKCδ phosphorylates TAp63 proteins at Thr157 to stabilize them and promote cell apoptosis.

Keywords: Apoptosis; PKCδ; TA isoforms of p63.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Apoptosis*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mutagenesis, Site-Directed
  • Mutant Proteins / chemistry
  • Mutant Proteins / metabolism
  • Neoplasms / metabolism*
  • Phosphorylation
  • Protein Interaction Domains and Motifs
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Kinase C / chemistry
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein Processing, Post-Translational
  • Protein Stability
  • Proto-Oncogene Proteins c-myc / chemistry
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Threonine / chemistry
  • Transcription Factors / agonists*
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Tumor Suppressor Proteins / agonists*
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism

Substances

  • MYC protein, human
  • Mutant Proteins
  • Protein Isoforms
  • Proto-Oncogene Proteins c-myc
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • TP53 protein, human
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Threonine
  • protein kinase C gamma
  • Protein Kinase C