Li S, Hunger S P
Section of Pediatric Hematology/Oncology, University of Colorado Cancer Center and School of Medicine, 4200 East Ninth Ave., Denver, CO 80262, USA.
Gene. 2001 Jan 24;263(1-2):239-45. doi: 10.1016/s0378-1119(00)00565-5.
DBP, HLF and TEF comprise a distinct subfamily of mammalian bZIP proteins that plays an important role in regulation of tissue-specific gene expression, particularly in the liver. In this report we demonstrate that DBP contains a 38 amino acid TAD which is highly homologous to the HLF and TEF TADs that we have delineated previously. Deletion of this domain completely abrogates transcriptional activity of native DBP and GAL4-DBP fusion proteins. This domain functions as a modular TAD that is a potent transcriptional activator when fused to the GAL4 DBD. While DBP itself is a liver-specific transactivator, the DBP TAD is active in a variety of cell types, indicating that liver-specific activity is not an intrinsic property of the TAD and must be conferred by other regions of the protein. Using GAL4-HLF fusion proteins, we further refine the core TAD of PAR proteins to a region of 13 amino acids. Recently described PAR-bZIP proteins from Drosophila and zebrafish also contain domains that share strong homology with the TAD of mammalian PAR proteins, making this one of the most highly evolutionarily conserved TADs identified to date.
DBP、HLF和TEF构成了哺乳动物bZIP蛋白的一个独特亚家族，在组织特异性基因表达的调控中发挥重要作用，尤其是在肝脏中。在本报告中，我们证明DBP包含一个38个氨基酸的转录激活结构域（TAD），它与我们之前描绘的HLF和TEF的TAD高度同源。缺失该结构域会完全消除天然DBP和GAL4-DBP融合蛋白的转录活性。该结构域作为一个模块化的TAD，当与GAL4 DNA结合结构域（DBD）融合时是一种有效的转录激活剂。虽然DBP本身是一种肝脏特异性反式激活因子，但DBP的TAD在多种细胞类型中都有活性，这表明肝脏特异性活性不是TAD的固有特性，必须由蛋白质的其他区域赋予。使用GAL4-HLF融合蛋白，我们进一步将PAR蛋白的核心TAD细化到一个13个氨基酸的区域。最近描述的来自果蝇和斑马鱼的PAR-bZIP蛋白也包含与哺乳动物PAR蛋白的TAD具有高度同源性的结构域，使其成为迄今为止鉴定出的进化上最保守的TAD之一。
