Pin1 and JNK1 cooperatively modulate TAp63γ

FEBS Open Bio. 2021 Mar;11(3):890-897. doi: 10.1002/2211-5463.13109. Epub 2021 Feb 19.


The p63 gene encodes at least 10 isoforms, which can be classified into TA and ∆N isotypes (TAp63 and ∆Np63 proteins) according to their differences at the N termini. TAp63γ is an important transcription factor. We previously reported that peptidyl-prolyl isomerase (PPI) Pin1 directly binds to TAp63γ protein and identified that serine 12 (S12 ) in the transactivation domain (TAD) of TAp63γ is required for regulation of its transcriptional activity. In the present study, we report that Pin1 stimulates transcriptional and pro-apoptotic activities of TAp63γ; this Pin1-mediated stimulation may depend on phosphorylation of S12 mediated by JNK1 and results in striking activation of TAp63γ. JNK1 represses transactivity of TAp63γ in cells without abundant Pin1 proteins and enhances it in the presence of sufficient levels of Pin1. Collectively, our data suggest a novel mechanism for regulation of TAp63γ transactivity: TAp63γ with unphosphorylated S12 is moderately active, phosphorylation at this residue (pS12 ) makes it hypoactive, and Pin1 binds to the pS12 -P13 motif and makes TAp63γ hyperactive. Our findings will aid in the elucidation of the mechanism underlying modulation of TAp63γ.

Keywords: JNK1; Pin1; TAp63γ; transactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Mitogen-Activated Protein Kinase 8 / metabolism*
  • Mutation
  • NIMA-Interacting Peptidylprolyl Isomerase / metabolism*
  • Phosphorylation
  • Protein Domains
  • Serine / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*


  • NIMA-Interacting Peptidylprolyl Isomerase
  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Serine
  • Mitogen-Activated Protein Kinase 8
  • PIN1 protein, human