Feng Weiguo, Williams Trevor
Department of Craniofacial Biology and Cellular and Structural Biology, BRB151, Campus Box C286, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, CO 80262, USA.
Mol Cell Neurosci. 2003 Oct;24(2):460-75. doi: 10.1016/s1044-7431(03)00209-4.
Members of the mammalian AP-2 transcription factor family have critical regulatory roles in many aspects of development and are also implicated in cancer progression. Four AP-2 genes have been previously characterized in mouse and human, encoding the AP-2alpha, AP-2beta, AP-2gamma, and AP-2delta proteins. Here we report the cloning and characterization of the fifth member of the vertebrate AP-2 family, AP-2epsilon. The AP-2epsilon protein is very similar to the other family members in its DNA binding and dimerization domain and also contains conserved proline and aromatic amino acid residues in the activation domain. Consistent with these observations, AP-2epsilon can bind to the GC-rich AP-2 consensus sequence and can dimerize either with itself or with any of the other AP-2 proteins. The AP-2epsilon protein is also able to activate transcription in a binding site-dependent manner. However, the mouse AP-2epsilon gene is distinctive from the other AP-2 genes in its pattern of expression during embryogenesis. Unlike AP-2alpha, AP-2beta, and AP-2gamma, transcripts corresponding to AP-2epsilon are not found in the neural crest and its derivatives. Instead, AP-2epsilon is expressed most prominently in the mitral cell layer of the developing olfactory bulb. A comparison of AP-2 gene family expression in the olfactory system suggests both distinct and overlapping functions for these transcription factors in forebrain development.
哺乳动物AP - 2转录因子家族的成员在发育的许多方面都起着关键的调节作用,并且也与癌症进展有关。先前已在小鼠和人类中鉴定出四个AP - 2基因,它们编码AP - 2α、AP - 2β、AP - 2γ和AP - 2δ蛋白。在此,我们报告脊椎动物AP - 2家族第五个成员AP - 2ε的克隆和特征。AP - 2ε蛋白在其DNA结合和二聚化结构域与其他家族成员非常相似,并且在激活结构域中也含有保守的脯氨酸和芳香族氨基酸残基。与这些观察结果一致,AP - 2ε可以结合富含GC的AP - 2共有序列,并且可以与自身或任何其他AP - 2蛋白二聚化。AP - 2ε蛋白也能够以结合位点依赖的方式激活转录。然而,小鼠AP - 2ε基因在胚胎发育过程中的表达模式与其他AP - 2基因不同。与AP - 2α、AP - 2β和AP - 2γ不同,在神经嵴及其衍生物中未发现与AP - 2ε对应的转录本。相反,AP - 2ε在发育中的嗅球的二尖瓣细胞层中表达最为突出。嗅觉系统中AP - 2基因家族表达的比较表明,这些转录因子在前脑发育中具有不同但又重叠的功能。