Nucleic Acids Research, 2001, Vol. 29, No. 22 4530-4540
© 2001 Oxford University Press
A minimal Bcl-x promoter is activated by Brn-3a and repressed by p53
Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK and 1CRC Wessex Medical Oncology Unit, Cancer Sciences Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK
The Brn-3a transcription factor stimulates the expression of the anti-apoptotic Bcl-2 and Bcl-x proteins and protects neuronal cells from apoptosis. Here we show that a minimal Bcl-x promoter is activated by Brn-3a and that this stimulation is prevented by the pro-apoptotic p53 protein. Both these effects are mediated via Bcl-x promoter sequences, which are indistinguishable from those required for minimal basal promoter activity. A newly described upstream Bcl-x promoter is also activated by Brn-3a with this activation being prevented by p53. Hence, Brn-3a-mediated activation of two distinct Bcl-x promoters and of the Bcl-2 promoter is blocked by p53 whereas this is not observed for Brn-3a activated promoters derived from genes not involved in inhibiting apoptosis. p53 therefore appears to specifically target the activation by Brn-3a of promoters derived from genes with an anti-apoptotic effect and this may be involved in the pro-apoptotic activity of p53.
* To whom correspondence should be addressed. Tel: +44 20 7905 2189; Fax: +44 20 7242 8437; Email: d.latchman{at}ich.ucl.ac.uk
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