TY - JOUR
T1 - δEF1 repressor controls selectively p53 family members during differentiation
AU - Fontemaggi, Giulia
AU - Gurtner, Aymone
AU - Damalas, Alexander
AU - Costanzo, Antonio
AU - Higashi, Yujiro
AU - Sacchi, Ada
AU - Strano, Sabrina
AU - Piaggio, Giulia
AU - Blandino, Giovanni
PY - 2005/11/12
Y1 - 2005/11/12
N2 - 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 δEF1/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 δEF1 on p73 regulatory regions was found between proliferating and differentiating muscle cells. We also found that δEF1 plays a role in the transcriptional regulation of p53 family members during keratinocytic differentiation. Mouse embryo fibroblasts derived from δEF1-deficient mice exhibit unbalanced expression of ΔNp63, TAp73 and ΔNp73 but not of TAp63 and p53. The analysis of tissues derived from δEF1+/- mice exhibit a selective enrichment of ΔNp63 in skin.
AB - 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 δEF1/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 δEF1 on p73 regulatory regions was found between proliferating and differentiating muscle cells. We also found that δEF1 plays a role in the transcriptional regulation of p53 family members during keratinocytic differentiation. Mouse embryo fibroblasts derived from δEF1-deficient mice exhibit unbalanced expression of ΔNp63, TAp73 and ΔNp73 but not of TAp63 and p53. The analysis of tissues derived from δEF1+/- mice exhibit a selective enrichment of ΔNp63 in skin.
KW - δEF1 transcriptional repressor
KW - p53 family
KW - p63
KW - p73
UR - http://www.scopus.com/inward/record.url?scp=27744451460&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=27744451460&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208891
DO - 10.1038/sj.onc.1208891
M3 - Article
C2 - 16007124
AN - SCOPUS:27744451460
VL - 24
SP - 7273
EP - 7280
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 49
ER -