Regulating P53 Activity in Cancer Cells

The protein BRD7 activates p53 and could therefore suppress the development of cancerous tumours, reports a study online in Nature Cell Biology this week. The transcription factor p53 is a critically important tumour suppressor protein, as inactivation of the p53 pathway contributes to the development of cancer. BRD7 expression is frequently lost in breast cancer, but it is currently not clear how BRD7 might inhibit tumour formation. Reuven Agami and colleagues show that BRD7 binds to and activates p53. BRD7 also regulates chromatin structure at p53-target genes, enabling more efficient transcription at these sites. As such, BRD7 loss permits oncogenic transformation of cultured human cells.

The researchers analyzed over two hundred human breast cancer samples and found that BRD7 expression was lost only in those tumours that contained functional p53. These findings suggest that selective BRD7 loss in human cancers provides an additional means of silencing the p53 pathway, and provide insight into how p53 transcriptional activity is regulated.

Author contact:
Reuven Agami (The Netherlands Cancer Institute, Amsterdam, Netherlands)E-mail: r.agami@nki.nl