Bennetts Jennifer S, Fowles Lindsay F, Berkman Jennifer L, van Bueren Kelly Lammerts, Richman Joy M, Simpson Fiona, Wicking Carol
Institute for Molecular Bioscience, The University of Queensland, St Lucia 4072, QLD 4072, Australia.
Gene. 2006 Jun 7;374:153-65. doi: 10.1016/j.gene.2006.01.027. Epub 2006 Mar 20.
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.
Cdca4（Hepp）最初被鉴定为一个在造血祖细胞而非造血干细胞中特异性表达的基因。最近的研究表明，它能刺激p53活性，并且在过表达时还会导致不依赖p53的生长抑制。我们在基于基因组表达的筛选中独立分离出了参与哺乳动物颅面发育的小鼠Cdca4基因，并表明Cdca4在小鼠胚胎发育过程中以时空受限的模式表达。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。与来自一系列物种的少数蛋白质一起，预测的CDCA4蛋白除了含有细胞周期蛋白A结合区域和PHD溴结构域结合区域的同源性外，还包含一个新的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此前已与细胞周期进程和染色质重塑相关联。通过计算机数据库挖掘，我们扩展了已知SERTA结构域蛋白的进化保守直系同源物的数量，并鉴定出了SERTA结构域家族的一个未表征成员SERTAD4，迄今为止在人类、小鼠、大鼠、狗、牛、河豚和鸡中都有直系同源物。在哺乳动物细胞中对瞬时和稳定转染的表位标记的CDCA4蛋白进行免疫定位表明，它在细胞周期的所有阶段主要定位于细胞核中。
