Molecular characterization of the zebrafish PEA3 ETS-domain transcription factor

Molecular characterization of the zebrafish PEA3 ETS-domain transcription factor
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DOI:
10.1038/sj.onc.1201911
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发表时间:
1998-07-09
期刊:
影响因子:
8
通讯作者:
Sharrocks, AD
Sharrocks, AD
中科院分区:
医学1区
文献类型:
--
作者:
Brown, LA;Amores, A;Sharrocks, AD

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PEA3亚家族的Ets结构域蛋白在调节转录激活方面发挥重要作用,并与多种肿瘤发生过程有关。在这里,我们描述了从斑马鱼中鉴定出这个家族的另一个成员,它很可能代表PEA3的同源物,在ETS DNA结合区和酸性转录激活域中观察到高度的序列保守性。斑马鱼PEA3的DNA结合特异性与哺乳动物家族成员基本相同,并受顺式作用抑制域的自身调节。斑马鱼PEA3的转录激活被ERK蛋白激酶和蛋白激酶A途径增强。在胚胎发育过程中,PEA3在中胚层体节和外胚层组织中都有复杂的时空表达模式,包括脑、脊髓背索和神经脊。我们对斑马鱼PEA3的特征进一步加深了我们对其分子功能的理解,其表达谱表明在早期脊椎动物胚胎的细胞模式中扮演了一个新的角色。
The PEA3 subfamily of ETS-domain proteins play important roles in regulating transcriptional activation and have been implicated in several tumorigenic processes. Here we describe the identification of a further member of this family from zebrafish which most likely represents a homologue of PEA3, A high degree of sequence conservation is observed in the ETS DNA-binding domain and acidic transcriptional activation domain. The DNA binding specificity of zebrafish PEA3 is virtually identical to that exhibited by mammalian family members and is autoregulated by cisacting inhibitory domains. Transcriptional activation by zebrafish PEA3 is potentiated by the ERK MAP kinase and protein kinase A pathways. During embryogenesis, PEA3 is expressed in complex spatial and temporal patterns in both mesodermal somites and ectodermal tissues including the brain, dorsal spinal chord and neural crest. Our characterisation of zebrafish PEA3 furthers our understanding of its molecular function and its expression profile suggests a novel role in cell patterning in the early vertebrate embryo.