TRP53 activates a global autophagy program to promote tumor suppression

Autophagy. 2013 Sep;9(9):1440-2. doi: 10.4161/auto.25833. Epub 2013 Jul 29.


The mechanisms by which the TP53/TRP53 transcription factor acts as a tumor suppressor remain incompletely understood. To gain new insights into TP53/TRP53 biology, we used ChIP-seq and RNA-seq technologies to define global TRP53 transcriptional networks in primary cells subjected to DNA damage. Intriguingly, we identified a TRP53-regulated autophagy program, which can be coordinately regulated by the TRP53 family members TRP63 and TRP73 in certain settings. While autophagy is not involved in TRP53-dependent cell cycle arrest, it contributes to both TRP53-driven apoptosis in response to DNA damage and TRP53-mediated transformation suppression. Collectively, our genome-wide analyses reveal a profound role for TRP53 in regulating autophagy, through an extensive transcriptional network, and have demonstrated an important role for this program in promoting TRP53-mediated apoptosis and tumor suppression.

Keywords: ChIP-seq; RNA-seq; apoptosis; autophagy; p53; tumor suppression.

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy*
  • Cell Cycle
  • DNA Damage
  • DNA-Binding Proteins / metabolism
  • Humans
  • Mice
  • Models, Biological
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Nuclear Proteins / metabolism
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins / metabolism


  • DNA-Binding Proteins
  • Nuclear Proteins
  • Trp73 protein, mouse
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins