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斑马鱼PEA3 ETS结构域转录因子的分子特征

Molecular characterization of the zebrafish PEA3 ETS-domain transcription factor.

作者信息

Brown L A, Amores A, Schilling T F, Jowett T, Baert J L, de Launoit Y, Sharrocks A D

机构信息

Department of Biochemistry and Genetics, The Medical School, University of Newcastle upon Tyne, UK.

出版信息

Oncogene. 1998 Jul 9;17(1):93-104. doi: 10.1038/sj.onc.1201911.

Abstract

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.

摘要

ETS 结构域蛋白的 PEA3 亚家族在调节转录激活中发挥重要作用,并与多种肿瘤发生过程有关。在此,我们描述了从斑马鱼中鉴定出该家族的另一个成员,它很可能是 PEA3 的同源物。在 ETS DNA 结合结构域和酸性转录激活结构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几乎相同,并由顺式作用抑制结构域进行自我调节。斑马鱼 PEA3 的转录激活由 ERK MAP 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(包括脑、背脊髓和神经嵴)中以复杂的空间和时间模式表达。我们对斑马鱼 PEA3 的表征进一步加深了我们对其分子功能的理解,其表达谱表明它在早期脊椎动物胚胎的细胞模式形成中具有新的作用。

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