The SCAN Family: Characterization of ZNF174

描述(由申请人提供)：在搜索负向调节器时 生长因子基因的表达，本课题组克隆了一个新的锌指转录 因子，命名为ZNFI74。试析开放阅读框架 揭示了两种类型的守恒元。第一个这样的结构是 三种常见的Cys2-His2(C2H2)型锌指，而第二种是 新的扩展基序，我们将其命名为扫描结构域。扫描域是一种 高度保守的80个氨基酸的模块化元件，存在于一个 超过50个人类Cys2-His2(C2H2)锌指蛋白。像亮氨酸一样 拉链，扫描域似乎控制着扫描域的关联 含有蛋白质的非共价多亚单位复合体，可能是 在这些稀有化中潜在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，该领域 在扫描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识别特性或 不同的监管活动，从而扩大了家庭的曲目。 只有几个扫描家族成员被描述了特征，但最初的 研究结果表明，这些基因在发育和 差异化。尽管这个家庭的成员数量很多，但值得注意的是 对于域本身或大多数 由结构域定义的蛋白质。为了调查这个家庭，我们提出了三个 特定的目的是定义ZNF174并表征扫描结构域。特定目标 1：进一步描述扫描家族的创始成员ZNF174； 特定目标2：确定与ZNF174扫描相互作用的蛋白质 领域；具体目标3：进一步表征ZNF 174扫描的能力 结构域来抑制DNA结合。总的来说，这些研究应该界定这一点 转录因子，并提供对大量 由Scan结构域定义的C2H2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.