The SCAN Family: Characterization of ZNF174

SCAN 系列：ZNF174 的表征

• 批准号: 6552994
• 负责人: Tucker O Collins
• 金额: $ 23.23万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6552994
• 关键词: DNA binding protein; antibody; binding sites; cell differentiation; complementary DNA; dimer; gel mobility shift assay; gene expression; gene induction /repression; genetic regulation; genetic regulatory element; liquid chromatography mass spectrometry; molecular cloning; platelet derived growth factor; polymerase chain reaction; protein localization; protein protein interaction; protein sequence; protein structure function; tissue /cell culture; transcription factor; yeast two hybrid system

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.

描述（由申请人提供）：寻找负调控因子 生长因子基因表达，我们组克隆了新的锌指转录 因子，被指定为 ZNFI74。开放阅读框分析 揭示了两种类型的保守元素。这些结构中的第一个是 三个一致的 Cys2-His2 (C2H2) 型锌指，而第二个是 新颖的扩展基序，我们将其命名为 SCAN 结构域。 SCAN 域是 高度保守的 80 个氨基酸模块元件，存在于一个家族中 超过 50 种人类 Cys2-His2 (C2H2) 锌指蛋白。就像亮氨酸一样 zipper，SCAN域似乎控制SCAN域的关联 含有蛋白质的非共价多亚基复合物，可能是 这些寡聚化中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域 在 SCAN 蛋白质家族中产生组合多样性。 异二聚体的形成可能会导致新的 DNA 识别特性或 不同的监管活动，从而扩大了家庭的范围。 只有少数 SCAN 家族成员已被表征，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人数众多，但值得注意的是 人们对域本身或大多数域的功能知之甚少 由域定义的蛋白质。为了调查这个家庭，我们提出了三个 具体目标是定义 ZNF174 并表征 SCAN 域。具体目标 1：进一步表征SCAN家族创始成员ZNF174； 具体目标 2：确定与 ZNF174 SCAN 相互作用的蛋白质 领域;具体目标 3：进一步表征 ZNF 174 SCAN 的能力 域抑制 DNA 结合。总的来说，这些研究应该定义这一点 转录因子并提供对大量转录因子的机制见解 由 SCAN 结构域定义的 C2H2 型锌指蛋白。