STAT1 regulates p73-mediated Bax gene expression

Soond, Surinder M.; Carroll, Christopher; Townsend, Paul A.; Sayan, Emre; Melino, Gerry; Behrmann, Iris; Knight, Richard A.; Latchman, David S.; Stephanou, Anastasis

doi:10.1016/j.febslet.2007.02.049

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Volume 581, Issue 6 , Pages 1217-1226, 20 March 2007

STAT1 regulates p73-mediated Bax gene expression

Edited by Varda Rotter

Surinder M. Soond
- Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
- Corresponding author. Fax: +44 0 207 905 2301.
Christopher Carroll
- Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
Paul A. Townsend
- Human Genetics Division, University of Southampton, Duthie Building, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
- Fax: +44 23 8079 4264.
Emre Sayan
- MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK
- Fax: +44 116 252 5616.
Gerry Melino
- MRC Toxicology Unit, Hodgkin Building, University of Leicester, Lancaster Road, Leicester LE1 9HN, UK
- Fax: +44 116 252 5616.
Iris Behrmann
- Laboratoire de Biologie et Physiologie Intégrée, Fac. Sciences, Techno. & Com., Université du Luxembourg, 162A, avenue de la Faı¨encerie, L-1511, Luxembourg
- Fax: +352 466 644 435.
Richard A. Knight
- Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
David S. Latchman
- Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK
Anastasis Stephanou
- Medical Molecular Biology Unit, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK

Received 5 January 2007; received in revised form 16 February 2007; accepted 22 February 2007. published online 02 March 2007.

Abstract

Although signal transducer and activator of transcription 1 (STAT1) mediated regulation of p53 transcription and apoptosis has been previously reported, modulation of other members of the p53 family of transcription factors remains poorly understood. In this study, we found that STAT1 and TA-p73 can interact directly and that p73-mediated Bax promoter activity was observed to be reduced by STAT1 expression in a p53-independent manner for which STAT1 Tyrosine-701 and Serine-727 are key residues. This study presents the first report physically linking STAT1 and TA-p73 signalling and highlights the modulation of the Bax promoter in the context of IFN-γ stimulation.

Abbreviations: STAT1, signal transducer and activator of transcription 1, MEF, murine embryonic fibroblast, IFN-γ, interferon-gamma, GST, glutathione S-transferase, PBS, phosphate-buffered saline, aa, amino acids