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Brn-3a Transcription Factor binds p73 to regulate survival and cell cycle arrest in neuronal cells

Chantelle Hudson, GM; A Emre Sayan, DSLAB-M; V, ; (2006) Brn-3a Transcription Factor binds p73 to regulate survival and cell cycle arrest in neuronal cells. Molecular and Cellular Biology

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Abstract

Brn-3a POU transcription factor is critical for survival and differentiation of specific sensory neurons during development or upon injury. It mediates its effects by regulating expression of survival genes, either directly or indirectly by interaction with other proteins. In this study, we demonstrated the physical interaction of Brn-3a with different p73 isoforms and showed co-localization in sensory neurons arising from the neural crest. The biological effects of p73/ Brn-3a interaction depended on the particular p73 isoform since co-expression of Brn-3a with TAp73 enhanced cell cycle arrest, whereas Brn-3a and Np73 cooperated to offer better protection from apoptosis. Interestingly Brn-3a antagonized TAp73 transactivation of pro-apoptotic Bax, but co-operated to increase transcription of the cell cycle regulator p21CIP1/Waf1. A further level of control for transactivation of pro-apoptotic bax required 425-494 aa within TAp73 C-terminus and this region was critical for Brn-3a to repress bax but not for cooperation on p21CIP1/Waf1 promoter. Results suggest that co-factors binding to p73 C-terminus facilitate maximal activation on the bax but not p21CIP1/Waf1 promoter and that Brn-3a modulated this interaction. Thus the physical interaction of Brn-3a with specific p73 isoforms will be critical for determining cell fate during neuronal development or in injured neurons expressing both factors.

Type: Article
Title: Brn-3a Transcription Factor binds p73 to regulate survival and cell cycle arrest in neuronal cells
Keywords: apoptosis/ Brn-3a/ neuronal differentiation / p73 /transcription
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Pre-clinical and Fundamental Science
URI: http://discovery.ucl.ac.uk/id/eprint/40709
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