CASH: A NOVEL BHLH PROTEIN: ROLE IN GENE TRANSCRIPTION

调节基因转录的蛋白质已经被识别出来， 根据常见的结构主题进行表征和分类。一 在不断增长的转录因子家族中发现的基序是 基本螺旋-环-螺旋(BHLH)结构域。表现血型黄体生成素的蛋白质 域参与小区规范的规范和 差异化。例如，果蝇的蛋白质 复杂，调节神经元发育。编码一部小说的CDNA克隆 与这些蛋白同源的BHLH超家族成员 是从斑点叉尾鱼(Ictalurus Marktatus)的嗅觉上皮中分离出来的 C DNA文库。这种名为CASH(叉尾)的BHLH蛋白 同源物)特别有趣，因为嗅觉上皮含有 具有连续分裂分化能力的神经元前体细胞 形成嗅觉神经元。鉴于BHLH转录的作用 因子在细胞规格和分化的调节中发挥作用， 本提案将研究和表征这种BHLH蛋白及其作用 在调节基因表达方面发挥作用。为了实现这一目标，我们计划； -确定Cash mRNA的组织和细胞分布；表达 用于免疫细胞化学抗血清生产的Cash BHLH蛋白 定位和功能研究；确定DNA序列基序以 Cash BHLH蛋白与其结合；表征同源和异构体 现金蛋白的蛋白质-蛋白质相互作用；评估 翻译后对该蛋白质活性的修饰； 识别和表征Cash蛋白与之相互作用的基因 并评估它们是如何受到监管的；确定是否有其他相关 硬骨鱼和其他脊椎动物嗅觉粘膜中的BHLH蛋白。 这将扩大对BHLH转录因子家族的了解 并促进我们对这些的分子基础的理解 蛋白质调节基因转录。关于北京和睦家医院的详细知识 蛋白质及其调控基因的正常机制 转录对于理解基因中的干扰是至关重要的 转录导致代谢性和退行性疾病相关 随着年龄的增长，肿瘤的发生，以及对创伤的反应。这项研究， 再加上神经科学和分子生物学的课程，威尔 提升申请者的技能，成为她不可或缺的桥梁 作为独立调查员的过程和发展，以便她可以 最终获得学术地位，从事独立研究 研究神经系统中的基因调控。

Proteins regulating gene transcription have been identified, characterized, and classified based on common structural motifs. One motif identified in a growing family of transcription factors is the basic helix-loop-helix (bHLH) domain. Proteins manifesting the BHLH domain participate in the regulation of cell specification and differentiation. For example proteins from the Drosophila achaete-scute complex, regulate neuronal development. A CDNA clone encoding a novel member of the BHLH protein superfamily homologous to these proteins has been isolated from a catfish (Ictalurus punctatus) olfactory epithelium CDNA library. This BHLH protein, named CASH (catfish achaete-acute homolog) is particularly interesting as olfactory epithelium contains neuronal precursors capable of continuous division and differentiation to form olfactory neurons. In light of the role that BHLH transcription factors play in the regulation of cell specification and differentiation, this proposal will study and characterize this BHLH protein and the role in plays in regulating gene expression. To achieve this we plan to; -determine the tissue and cell distribution of the CASH MRNA; express the CASH BHLH protein for antiserum production for immunocytochemical localization and functional studies; identify the DNA sequence motif to which the CASH BHLH protein binds; characterize homo- and heteromeric protein-protein interactions of the CASH protein; evaluate the role of post-translational modifications on the activities of this proteins; identify and characterize the genes that the CASH protein interacts with and evaluate how they are regulated; determine if there are other related BHLH proteins in olfactory mucosa of teleosts and other vertebrates. This will expand knowledge of the BHLH family of transcription factors and advance our understanding of the molecular basis by which these proteins regulate gene transcription. Detailed knowledge of BHLH proteins and the normal mechanisms by which they regulate gene transcription is critical in understanding how disturbances in gene transcription result in metabolic and degenerative diseases associated with aging, oncogenesis, and in response to trauma. This research, coupled with coursework in neuroscience and molecular biology, will upgrade the applicant's skills and serve as an essential bridge for her process and development as an independent investigator so that she may eventually obtain an academic position to pursue independent research studying gene regulation in the nervous system.