The Brn-3a POU family transcription factor stimulates p53 gene expression in human and mouse tumour cells

Neurosci Lett. 2002 Dec 6;334(1):1-4. doi: 10.1016/s0304-3940(02)00813-3.


The Brn-3a POU family transcription factor is able to induce the expression of genes encoding anti-apoptotic proteins such as Bcl-2 and Bcl-x and protects neuronal cells from apoptosis. This effect is opposed by the pro-apoptotic p53 protein which completely inhibits the ability of Brn-3a to activate the Bcl-2 and Bcl-x promoters. Here we demonstrate that Brn-3a is able to stimulate p53 expression. Thus, in co-transfection experiments, Brn-3a activates the p53 promoter acting via a region from +22 to +67, located between the most proximal (+1) and the most distal (+105) transcriptional start sites. Similarly, reduction of Brn-3a expression using anti-sense constructs reduces endogenous p53 expression in human neuroblastoma or cervical carcinoma cell lines growing in vitro and as tumours in nude mice whilst increasing Brn-3a levels enhances p53 expression. These results suggest the existence of a negative feedback loop in which elevated Brn-3a expression induces the expression of p53 which, in turn, antagonises the anti-apoptotic activity of Brn-3a.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Apoptosis / physiology
  • Carcinoma, Squamous Cell
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics*
  • Humans
  • Mice
  • Mice, Nude
  • Neuroblastoma
  • Promoter Regions, Genetic
  • Transcription Factor Brn-3
  • Transcription Factor Brn-3A
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Transcription Factors / physiology
  • Transcriptional Activation / genetics*
  • Transcriptional Activation / physiology
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics*


  • DNA-Binding Proteins
  • POU4F1 protein, human
  • Pou4f1 protein, mouse
  • Transcription Factor Brn-3
  • Transcription Factor Brn-3A
  • Transcription Factors
  • Tumor Suppressor Protein p53