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Zinc finger proteins involved in neuronal development

锌指蛋白参与神经元发育

基本信息

批准号：
8501705
负责人：
Angelique Nicole Besold
金额：
$ 2.88万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8501705
关键词：
Address Alzheimer&apos s Disease Binding Biochemical Brain Brain Neoplasms Cerebral Palsy DNA DNA Binding Development Disease Enabling Factors Fingers Fluorescence Anisotropy Genes Homeostasis Human Genome Ischemia Lead Link Malignant Neoplasms Malignant neoplasm of brain Mediating Membrane Mental Retardation Metals Methodology Molecular Multiple Sclerosis Lesions Mutation Myelin Nervous System Physiology Nervous system structure Neuraxis Neurons Nucleic Acid Binding Oligodendroglia Periventricular Leukomalacia Play Property Proteins Rattus Role Schizophrenia Sequence Homology Spectrum Analysis Stroke Structure Techniques Transcriptional Regulation Zinc Zinc Fingers Zinc deficiency biological systems cell type insight nervous system disorder neuron development oligodendroglioma protein folding protein structure function relating to nervous system transcription factor zinc-binding protein

项目摘要

DESCRIPTION (provided by applicant): Zinc plays a crucial role in development, particularly in the brain where it is found at high concentrations. Zinc levels must be tightly controlled as disruption of zinc homeostasis has been linked to a variety of disorders ranging from Alzheimer's disease to ischemia induced by cerebral stroke to schizophrenia. Most zinc in the brain is found bound to proteins, including zinc finger transcription factors. Two zinc finger transcription factors that play a crucial role in neuronal development are Neural Zinc Finger Factor-1 (NZF-1) and Myelin Transcription Factor 1 (MyT1). These proteins are essential for the development of neurons and oligodendrocytes, respectively and misregulation of these proteins has been associated brain cancer, schizophrenia, and mental retardation. Despite their importance in neuronal development, relatively little is known about the structure/function of these proteins. Both NZF-1 and MyT1 contain multiple, homologous zinc binding domains yet recognize and regulate completely different genes. This proposal is aimed at identifying the factors that enable the two proteins to regulate different genes and at understanding the mechanism of zinc mediated DNA recognition. The following two aims are proposed: 1) What are the roles of the 5 zinc finger domains in NZF-1? and 2) What are the roles of the 6 zinc finger domains in MyT1 and how do these differ from those of NZF-1? A systematic approach, using biochemical and biophysical methodologies, will be taken. Understanding the fundamental biochemical and biophysical properties of these proteins will be a first step towards understanding how these highly homologous transcription factors function to regulate neuronal development and provide key insights into how misregulation may lead to neurological disorders.

描述（由申请人提供）：锌在发育中起着至关重要的作用，特别是在大脑中，它以高浓度存在。锌水平必须严格控制，因为锌稳态的破坏与从阿尔茨海默病到脑中风引起的缺血到精神分裂症的各种疾病有关。大脑中的大多数锌被发现与蛋白质结合，包括锌指转录因子。在神经元发育中起关键作用的两种锌指转录因子是神经锌指因子-1（NZF-1）和髓磷脂转录因子1（MyT 1）。这些蛋白质分别是神经元和少突胶质细胞发育所必需的，并且这些蛋白质的失调与脑癌、精神分裂症和精神发育迟滞相关。尽管它们在神经元发育中的重要性，但对这些蛋白质的结构/功能知之甚少。NZF-1和MyT 1都含有多个同源的锌结合结构域，但识别和调节完全不同的基因。该建议旨在确定使这两种蛋白质能够调节不同基因的因素，并了解锌介导的DNA识别机制。本研究的目的有两个：1）NZF-1中5个锌指结构域的功能是什么？2）MyT 1中6个锌指结构域的作用是什么，它们与NZF-1有何不同？将采用生物化学和生物物理方法学的系统办法。了解这些蛋白质的基本生物化学和生物物理特性将是了解这些高度同源的转录因子如何调节神经元发育的第一步，并提供有关失调如何导致神经系统疾病的关键见解。