Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription
Copyright policy )Brn-3a/POU4F1 interacts with and differentially affects p73-mediated transcription
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 DeltaNp73 cooperated to increase protection from apoptosis. Brn-3a antagonized TAp73 transactivation of pro-apoptotic Bax, but co-operated 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.
- University of Rome Tor Vergata Italy
- Istituti di Ricovero e Cura a Carattere Scientifico Italy
- University of Southampton United Kingdom
- University College London United Kingdom
- University of Leicester United Kingdom
Transcription, Genetic, Apoptosis, animal cell, protein binding, nerve cell differentiation, Mice, Protein Isoforms, rat, Promoter Regions, Genetic, bcl-2-Associated X Protein, Nuclear Protein, Neurons, cell fate, Transcription Factor Brn-3A, Tumor, article, Nuclear Proteins, protein function, Transcription Factor Brn-3B, DNA-Binding Proteins, priority journal, cell cycle arrest, Neural Crest, protein protein interaction, isoprotein, Promoter Regions (Genetics), transcription regulation, cell cycle regulation, neural crest, protein Bax, Human, Cyclin-Dependent Kinase Inhibitor p21, 570, cell protection, DNA-Binding Protein, Recombinant Fusion Proteins, cyclin dependent kinase inhibitor 1, transcription factor POU4F1, embryo, protein localization, protein p73, Cell Line, promoter region, transactivation, Cell Line, Tumor, sensory nerve cell, Animals, Humans, controlled study, amino acid derivative, Neurons, Afferent, protein expression, mouse, carboxy terminal sequence, nonhuman, Animal, Tumor Suppressor Proteins, Protein Isoform, Tumor Protein p73, Afferent, 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, Neuron, apoptosi, Rats, cell damage, protein determination
Transcription, Genetic, Apoptosis, animal cell, protein binding, nerve cell differentiation, Mice, Protein Isoforms, rat, Promoter Regions, Genetic, bcl-2-Associated X Protein, Nuclear Protein, Neurons, cell fate, Transcription Factor Brn-3A, Tumor, article, Nuclear Proteins, protein function, Transcription Factor Brn-3B, DNA-Binding Proteins, priority journal, cell cycle arrest, Neural Crest, protein protein interaction, isoprotein, Promoter Regions (Genetics), transcription regulation, cell cycle regulation, neural crest, protein Bax, Human, Cyclin-Dependent Kinase Inhibitor p21, 570, cell protection, DNA-Binding Protein, Recombinant Fusion Proteins, cyclin dependent kinase inhibitor 1, transcription factor POU4F1, embryo, protein localization, protein p73, Cell Line, promoter region, transactivation, Cell Line, Tumor, sensory nerve cell, Animals, Humans, controlled study, amino acid derivative, Neurons, Afferent, protein expression, mouse, carboxy terminal sequence, nonhuman, Animal, Tumor Suppressor Proteins, Protein Isoform, Tumor Protein p73, Afferent, 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, Neuron, apoptosi, Rats, cell damage, protein determination
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