JNK1 inhibits transcriptional and pro-apoptotic activity of TAp63γ

FEBS Lett. 2015 Nov 30;589(23):3686-90. doi: 10.1016/j.febslet.2015.10.028. Epub 2015 Nov 4.

Abstract

TAp63γ is a homologue of tumor suppressor p53 and functions as a transcriptional factor playing key roles in cell cycle and cell apoptosis. In the present work, we find that JNK1 can physically interact with N-terminal transactivation domain (TAD) of TAp63. Overexpression of JNK1 inhibits TAp63γ-mediated transcription, while knockdown or inhibition of endogenous JNK1 increases transactivity of TAp63γ. Further study reveals that Ser12 site in TAD is critical for JNK1-mediated inhibition of TAp63γ. This JNK1-mediated inhibition can impair pro-apoptotic activity of TAp63γ. Together, we report a novel regulation of TAp63γ transactivity and pro-apoptotic activity mediated by JNK1.

Keywords: Apoptosis; TAp63γ; Transactivity; c-Jun N-terminal kinase 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Gene Knockdown Techniques
  • HeLa Cells
  • Humans
  • Mitogen-Activated Protein Kinase 8 / deficiency
  • Mitogen-Activated Protein Kinase 8 / genetics
  • Mitogen-Activated Protein Kinase 8 / metabolism*
  • Protein Structure, Tertiary
  • Transcription Factors / chemistry
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transcriptional Activation
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / metabolism*

Substances

  • TP63 protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Mitogen-Activated Protein Kinase 8