δEF1 repressor controls selectively p53 family members during differentiation
δEF1 repressor controls selectively p53 family members during differentiation
The discovery of two new p53 homologs, p73 and p63, has defined a family of transcription factors heavily involved in the control of growth suppression, apoptosis, differentiation and development. While p53-deficient mice undergo spontaneous tumors, p73 and p63 knockout mice exhibit severe developmental defects. We demonstrate here that p73 gene is an in vivo transcriptional target of the muscle regulatory factors MyoD, myogenin, Myf5 and Myf6. Ectopic expression of the transcriptional repressor deltaEF1/ZEB/zfhx1a counteracts MyoD/Myf5- or MyoD/Myf6-mediated transcriptional activation of p73. A distinct pattern of in vivo recruitment of muscle regulatory factors and deltaEF1 on p73 regulatory regions was found between proliferating and differentiating muscle cells. We also found that deltaEF1 plays a role in the transcriptional regulation of p53 family members during keratinocytic differentiation. Mouse embryo fibroblasts derived from deltaEF1-deficient mice exhibit unbalanced expression of DeltaNp63, TAp73 and DeltaNp73 but not of TAp63 and p53. The analysis of tissues derived from deltaEF1+/- mice exhibit a selective enrichment of DeltaNp63 in skin.
- University of Rome Tor Vergata Italy
- Osaka University Japan
p53, Keratinocytes, Transcription Factor, Messenger, Mice, Genes, Tumor Suppressor, Cells, Cultured, Nuclear Protein, Mice, Knockout, Cultured, Reverse Transcriptase Polymerase Chain Reaction, Blotting, Nuclear Proteins, Homeodomain Protein, Zinc Fingers, Cell Differentiation, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Myogenic Regulatory Factors, Trans-Activator, Phosphoprotein, Fibroblast, Myogenin, Myogenic Regulatory Factor 5, Settore MED/35 - MALATTIE CUTANEE E VENEREE, Western, Tumor Suppressor, Keratinocyte, Human, Myogenic Regulatory Factor, Knockout, DNA-Binding Protein, Cells, Blotting, Western, Animals; Genes, Tumor Suppressor; Humans; Myogenic Regulatory Factor 5; Cell Proliferation; Myogenin; Fibroblasts; Mice, Knockout; Gene Expression Regulation, Neoplastic; Genes, p53; Nuclear Proteins; Phosphoproteins; Transcription Factors; Keratinocytes; Myogenic Regulatory Factors; Trans-Activators; Homeodomain Proteins; DNA-Binding Proteins; Cell Differentiation; Mice; MyoD Protein; Reverse Transcriptase Polymerase Chain Reaction; Tumor Suppressor Proteins; RNA, Messenger; Blotting, Western; Cells, Cultured; Zinc Fingers, Animals, Humans, Cell Proliferation, MyoD Protein, Homeodomain Proteins, Neoplastic, Tumor Suppressor Protein, Animal, Fibroblasts, Genes, p53, Genes, Gene Expression Regulation, RNA
p53, Keratinocytes, Transcription Factor, Messenger, Mice, Genes, Tumor Suppressor, Cells, Cultured, Nuclear Protein, Mice, Knockout, Cultured, Reverse Transcriptase Polymerase Chain Reaction, Blotting, Nuclear Proteins, Homeodomain Protein, Zinc Fingers, Cell Differentiation, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Myogenic Regulatory Factors, Trans-Activator, Phosphoprotein, Fibroblast, Myogenin, Myogenic Regulatory Factor 5, Settore MED/35 - MALATTIE CUTANEE E VENEREE, Western, Tumor Suppressor, Keratinocyte, Human, Myogenic Regulatory Factor, Knockout, DNA-Binding Protein, Cells, Blotting, Western, Animals; Genes, Tumor Suppressor; Humans; Myogenic Regulatory Factor 5; Cell Proliferation; Myogenin; Fibroblasts; Mice, Knockout; Gene Expression Regulation, Neoplastic; Genes, p53; Nuclear Proteins; Phosphoproteins; Transcription Factors; Keratinocytes; Myogenic Regulatory Factors; Trans-Activators; Homeodomain Proteins; DNA-Binding Proteins; Cell Differentiation; Mice; MyoD Protein; Reverse Transcriptase Polymerase Chain Reaction; Tumor Suppressor Proteins; RNA, Messenger; Blotting, Western; Cells, Cultured; Zinc Fingers, Animals, Humans, Cell Proliferation, MyoD Protein, Homeodomain Proteins, Neoplastic, Tumor Suppressor Protein, Animal, Fibroblasts, Genes, p53, Genes, Gene Expression Regulation, RNA
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