Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Western
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Cell Differentiation*
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Cell Proliferation
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Cells, Cultured
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Gene Expression Regulation, Neoplastic*
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Genes, Tumor Suppressor / physiology
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Genes, p53 / physiology
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Homeodomain Proteins / physiology*
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Humans
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Keratinocytes / cytology
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Keratinocytes / metabolism
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Mice
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Mice, Knockout
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MyoD Protein / genetics
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MyoD Protein / metabolism
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Myogenic Regulatory Factor 5 / genetics
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Myogenic Regulatory Factor 5 / metabolism
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Myogenic Regulatory Factors / genetics
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Myogenic Regulatory Factors / metabolism
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Myogenin / genetics
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Myogenin / metabolism
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Phosphoproteins / physiology
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RNA, Messenger
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Reverse Transcriptase Polymerase Chain Reaction
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Trans-Activators / physiology
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcription Factors / physiology*
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Tumor Protein p73
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Tumor Suppressor Proteins
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Zinc Finger E-box-Binding Homeobox 1
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Zinc Fingers
Substances
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DNA-Binding Proteins
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Homeodomain Proteins
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Myf5 protein, mouse
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MyoD Protein
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Myogenic Regulatory Factor 5
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Myogenic Regulatory Factors
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Myogenin
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Nuclear Proteins
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Phosphoproteins
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RNA, Messenger
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TP63 protein, human
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TP73 protein, human
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Trans-Activators
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Transcription Factors
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Trp73 protein, mouse
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Tumor Protein p73
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Tumor Suppressor Proteins
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ZEB1 protein, human
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Zfhx1a protein, mouse
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Zinc Finger E-box-Binding Homeobox 1
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delta Np73 protein, human
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myogenic factor 6