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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.

Type

Journal article

Journal

Neurosci Lett

Publication Date

06/12/2002

Volume

334

Pages

1 - 4

Keywords

Animals, Apoptosis, Carcinoma, Squamous Cell, DNA-Binding Proteins, Humans, Mice, Mice, Nude, Neuroblastoma, Promoter Regions, Genetic, Transcription Factor Brn-3, Transcription Factor Brn-3A, Transcription Factors, Transcriptional Activation, Transfection, Tumor Cells, Cultured, Tumor Suppressor Protein p53