The SCAN Family: Characterization of ZNF174

描述（由申请人提供）：在寻找负调节剂 生长因子基因的表达，我们的小组克隆了一个新的锌指转录 因子，其被指定为ZNFI 74。开放式阅读框架分析 揭示了两种类型的保守元件。这些建筑中的第一个是 三个共有Cys 2-His 2（C2 H2）型锌指，而第二个是一个共有的Cys 2-His 2（C2 H2）型锌指。 我们命名为SCAN结构域的新的扩展基序。SCAN域是一个 高度保守的80个氨基酸的模块化元件，其存在于一个家族中， 超过50种人Cys 2-His 2（C2 H2）锌指蛋白。比如亮氨酸 拉链，SCAN结构域似乎控制SCAN结构域的关联 含有蛋白质的非共价多亚基复合物， 在这些寡聚化的合作伙伴选择的主要机制 锌指转录因子。一个有吸引力的可能性是， 在SCAN蛋白质家族中产生组合多样性。 异源二聚体的形成可能导致新的DNA识别特性， 不同的调节活动，从而扩大家庭的剧目。 只有少数的SCAN家族成员的特征，但最初的 研究结果表明，这些基因在发育中发挥作用， 分化尽管这个家庭成员众多， 关于该领域本身或大多数领域的功能知之甚少。 由结构域定义的蛋白质为了调查这个家庭，我们提出三个 具体的目的是定义ZNF 174和表征SCAN结构域。具体目标 1：进一步表征SCAN家族的创始成员ZNF 174; 具体目标2：确定与ZNF 174 SCAN相互作用的蛋白质 具体目标3：进一步表征ZNF 174扫描的能力 结构域抑制DNA结合。总的来说，这些研究应该定义这一点， 转录因子，并提供了大量的机制的见解， 由SCAN结构域定义的C2 H2型锌指蛋白。

DESCRIPTION (provided by applicant): In a search for negative regulators of growth factor gene expression, our group cloned a new zinc finger transcription factor, which was designated ZNFI74. Analysis of the open reading frame revealed two types of conserved elements. The first of these structures were three consensus Cys2-His2 (C2H2) type zinc fingers, while the second was a novel extended motif which we designated the SCAN domain. The SCAN domain is a highly conserved 80 amino acid modular element that is found in a family of more than 50 human Cys2-His2 (C2H2) zinc finger proteins. Like the leucine zipper, the SCAN domain appears to control association of SCAN domain containing proteins into non-covalent, multisubunit complexes and may be the primary mechanism underlying partner choice in the oligomenzation of these zinc-finger transcription factors. An attractive possibility is that the domain generates combinatorial diversity within the SCAN family of proteins. Heterodimer formation could lead to novel DNA recognition properties or to different regulatory activities, thus expanding the repertoire of the family. Only a few of the SCAN family members have been characterized, but the initial findings suggest that these genes play roles in development and differentiation. Despite the number of members in this family, remarkably little is known about the domain itself or the functions of most of the proteins defined by the domain. To investigate this family, we propose three specific aims to define ZNF174 and characterize the SCAN domain. Specific Aim 1: To further characterize ZNF174, a founding member of the SCAN family; Specific Aim 2: To determine the proteins that interact with the ZNF174 SCAN domain; Specific Aim 3: To further characterize the ability of the ZNF 174 SCAN domain to inhibit DNA binding. Collectively, these studies should define this transcription factor and provide mechanistic insights into the large number of C2H2 type zinc finger proteins defined by the SCAN domain.