Evolutionary conservation and murine embryonic expression of the gene encoding the SERTA domain-containing protein CDCA4 (HEPP)
Evolutionary conservation and murine embryonic expression of the gene encoding the SERTA domain-containing protein CDCA4 (HEPP)
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DOI：
10.1016/j.gene.2006.01.027
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发表时间：
2006-06-07
期刊：
影响因子：
3.5
通讯作者：
Wicking, Carol
中科院分区：
文献类型：
--
作者：
Bennetts, Jennifer S.;Fowles, Lindsay F.;Wicking, Carol
Cdca4（Hepp）最初被鉴定为在造血祖细胞中特异性表达的基因，而不是造血干细胞。最近，它已被证明刺激p53活性，并导致p53非依赖性生长抑制时，过表达。我们独立地分离出鼠Cdca4基因在基因组表达为基础的筛选基因参与哺乳动物颅面发育，并表明，Cdca4在小鼠胚胎发育过程中的时空限制模式表达。除了在包括咽弓在内的面部原基中表达外，Cdca4还在发育中的肢芽、脑、脊髓、背根神经节、牙齿、眼睛和毛囊中表达。沿着来自一系列物种的少量蛋白质，预测的CDCA 4蛋白除了具有同源性的细胞周期蛋白A结合区和PHD溴结构域结合区之外还含有新的SERTA基序。虽然SERTA结构域的功能尚不清楚，但含有该结构域的蛋白质先前已与细胞周期进展和染色质重塑相关。使用计算机数据库挖掘，我们已经扩展了已知的SERTA结构域蛋白的进化保守的直向同源物的数量，并确定了一个未表征的成员的SERTA结构域家族，SERTAD4，直向同源物迄今在人类，小鼠，大鼠，狗，牛，河豚和鸡。瞬时和稳定转染的表位标记的CDCA 4蛋白在哺乳动物细胞中的免疫定位表明，它主要驻留在细胞周期的所有阶段的细胞核中。(c)2006 Elsevier B.V.保留所有权利。
Cdca4 (Hepp) was originally identified as a gene expressed specifically in hematopoietic progenitor cells as opposed to hematopoietic stem cells. More recently, it has been shown to stimulate p53 activity and also lead to p53-independent growth inhibition when overexpressed. We independently isolated the murine Cdca4 gene in a genomic expression-based screen for genes involved in mammalian craniofacial development, and show that Cdca4 is expressed in a spatio-temporally restricted pattern during mouse embryogenesis. In addition to expression in the facial primordia including the pharyngeal arches, Cdca4 is expressed in the developing limb buds, brain, spinal cord, dorsal root ganglia, teeth, eye and hair follicles. Along with a small number of proteins from a range of species, the predicted CDCA4 protein contains a novel SERTA motif in addition to cyclin A-binding and PHD bromodomain-binding regions of homology. While the function of the SERTA domain is unknown, proteins containing this domain have previously been linked to cell cycle progression and chromatin remodelling. Using in silico database mining we have extended the number of evolutionarily conserved orthologues of known SERTA domain proteins and identified an uncharacterised member of the SERTA domain family, SERTAD4, with orthologues to date in human, mouse, rat, dog, cow, Tetraodon and chicken. Immunolocalisation of transiently and stably transfected epitope-tagged CDCA4 protein in mammalian cells suggests that it resides predominantly in the nucleus throughout all stages of the cell cycle. (c) 2006 Elsevier B.V. All rights reserved.