deltaEF1 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.
Fontemaggi
Giulia
G
Department of Experimental Oncology, Regina Elena Cancer Institute, 00158 Rome, Italy.
Gurtner
Aymone
A
Damalas
Alexander
A
Costanzo
Antonio
A
Higashi
Yujiro
Y
Sacchi
Ada
A
Strano
Sabrina
S
Piaggio
Giulia
G
Blandino
Giovanni
G
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor / Q000502:physiology; D016158:Genes, p53 / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D051787:Myogenic Regulatory Factor 5 / Q000235:genetics / Q000378:metabolism; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D018008:Myogenin / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000502:physiology; D012333:RNA, Messenger; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D000071799:Zinc Finger E-box-Binding Homeobox 1; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D017570:MyoD Protein; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D000071799:Zinc Finger E-box-Binding Homeobox 1; C497418:Myf5 protein, mouse; C115051:TP63 protein, human; C000606460:TP73 protein, human; C000606368:Trp73 protein, mouse; C486307:ZEB1 protein, human; C000606369:delta Np73 protein, human; C063403:myogenic factor 6; C519422:ZEB1 protein, mouse