δEF1 repressor controls selectively p53 family members during differentiation
δEF1 repressor controls selectively p53 family members during differentiation
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DOI：
10.1038/sj.onc.1208891
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发表时间：
2005-11-01
期刊：
影响因子：
8
通讯作者：
Blandino, G
中科院分区：
文献类型：
--
作者：
Fontemaggi, G;Gurtner, A;Blandino, G
两个新的p53同源物p73和p63的发现，定义了一个转录因子家族，在很大程度上参与控制生长抑制、凋亡、分化和发育。p53缺失小鼠发生自发性肿瘤，而p73和p63敲除小鼠表现出严重的发育缺陷。我们在这里证明p73基因是肌肉调节因子MyoD、myogenin、Myf5和Myf6的体内转录靶点。转录抑制因子EF1/ZEB/ zfhx1a的异位表达可抵消MyoD/ myf5或MyoD/ Myf6介导的p73转录激活。在增殖和分化的肌肉细胞之间，肌肉调节因子和δ EF1在p73调节区域的体内募集有明显的模式。我们还发现dEF1在角化细胞分化过程中对p53家族成员的转录调控中发挥作用。老鼠胚胎。来自delta ef1缺陷小鼠的成纤维细胞表现出DNp63、TAp73和delta Np73的不平衡表达，但TAp63和p53的不平衡表达。来自delta EF1+/-小鼠的组织分析显示DNp63在皮肤中选择性富集。
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 delta EF1/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 delta EF1 on p73 regulatory regions was found between proliferating and differentiating muscle cells. We also found that dEF1 plays a role in the transcriptional regulation of p53 family members during keratinocytic differentiation. Mouse embryo. fibroblasts derived from delta EF1-deficient mice exhibit unbalanced expression of DNp63, TAp73 and Delta Np73 but not of TAp63 and p53. The analysis of tissues derived from delta EF1+/- mice exhibit a selective enrichment of DNp63 in skin.