The Brn-3a/POU4F1 POU transcription factor is critical for the survival and differentiation of specific sensory neurons during development or upon injury; by regulating expression of target genes, either directly or indirectly upon 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 depend on the particular p73 isoform, because co-expression of Brn-3a with TAp73 enhanced cell cycle arrest, whereas Brn-3a and DNp73 cooperated to increase protection from apoptosis. Brn-3a antagonized TAp73 transactivation of pro-apoptotic Bax, but cooperated to increase transcription of the cell cycle regulator p21(CIP1/Waf1). The region 425-494 amino acids within the TAp73 C terminus were critical for Brn-3a to repress Bax transactivation, but not for cooperation on the p21(CIP1/Waf1) promoter. Our results suggest that co-factors binding to the p73 C terminus facilitate maximal activation on the Bax but not p21(CIP1/Waf1) promoter and that Brn-3a modulates 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.

Hudson, C.d., Sayan, A.e., Melino, G., Knight, R.a., Latchman, D.s., Budhram Mahadeo, V. (2008). Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription. CELL DEATH AND DIFFERENTIATION, 15(8), 1266-1278 [10.1038/cdd.2008.45].

Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription

MELINO, GENNARO;
2008-01-01

Abstract

The Brn-3a/POU4F1 POU transcription factor is critical for the survival and differentiation of specific sensory neurons during development or upon injury; by regulating expression of target genes, either directly or indirectly upon 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 depend on the particular p73 isoform, because co-expression of Brn-3a with TAp73 enhanced cell cycle arrest, whereas Brn-3a and DNp73 cooperated to increase protection from apoptosis. Brn-3a antagonized TAp73 transactivation of pro-apoptotic Bax, but cooperated to increase transcription of the cell cycle regulator p21(CIP1/Waf1). The region 425-494 amino acids within the TAp73 C terminus were critical for Brn-3a to repress Bax transactivation, but not for cooperation on the p21(CIP1/Waf1) promoter. Our results suggest that co-factors binding to the p73 C terminus facilitate maximal activation on the Bax but not p21(CIP1/Waf1) promoter and that Brn-3a modulates 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.
2008
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/11 - BIOLOGIA MOLECOLARE
English
Con Impact Factor ISI
amino acid derivative; cyclin dependent kinase inhibitor 1; isoprotein; protein Bax; protein p73; transcription factor POU4F1; animal cell; apoptosis; article; carboxy terminal sequence; cell cycle arrest; cell cycle regulation; cell damage; cell fate; cell protection; controlled study; embryo; mouse; nerve cell differentiation; neural crest; nonhuman; priority journal; promoter region; protein binding; protein determination; protein expression; protein function; protein localization; protein protein interaction; rat; sensory nerve cell; transactivation; transcription regulation; Animals; Apoptosis; bcl-2-Associated X Protein; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p21; DNA-Binding Proteins; Humans; Mice; Neural Crest; Neurons; Neurons, Afferent; Nuclear Proteins; Promoter Regions (Genetics); Protein Isoforms; Rats; Recombinant Fusion Proteins; Transcription Factor Brn-3A; Transcription Factor Brn-3B; Transcription, Genetic; Tumor Suppressor Proteins
Hudson, C.d., Sayan, A.e., Melino, G., Knight, R.a., Latchman, D.s., Budhram Mahadeo, V. (2008). Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription. CELL DEATH AND DIFFERENTIATION, 15(8), 1266-1278 [10.1038/cdd.2008.45].
Hudson, Cd; Sayan, Ae; Melino, G; Knight, Ra; Latchman, Ds; Budhram Mahadeo, V
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/47811
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