HCF-1, A Mammalian Factor Controlling HSV Gene Expression

HCF-1，一种控制 HSV 基因表达的哺乳动物因子

• 批准号: 7592200
• 负责人: THOMAS M KRISTIE
• 金额: $ 63.97万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7592200
• 关键词: Biochemical; Cell Communication; Cell model; Cell physiology; Complex; DNA biosynthesis; Enhancers; Gene Expression; Genes; Genetic Transcription; Herpesviridae; Immediate-Early Genes; Laboratories; Life Cycle Stages; Lytic; Lytic Phase; Multiprotein Complexes; Proteins; Proteolytic Processing; Regulation; Regulatory Pathway; Role; Simplexvirus; Site; Tertiary Protein Structure; Transcription Coactivator; Transcriptional Regulation; Viral; Viral Proteins; Virus; host cell factor C1; insight; molecular modeling; protein protein interaction

The initiation of the herpes simplex virus lytic replication cycle depends upon the coordinated expression of the viral (IE) immediate early genes. These genes are controlled by a complex multiprotein enhancer assembly that consists of viral and cellular components. Studies of the various components, protein interactions, viral and cellular functions provides both a model for cellular transcriptional regulation as well as insights into the mechanisms utilized by the virus. The focus of the laboratory is the identification and characterization of the critical components of this regulatory pathway. The mammalian coactivator HCF-1 is one of the more complex factors involved in both the assembly of the enhancer complex and the activation of the IE genes. Studies focus upon both functions during the viral lytic cycle as well as in normal cellular processes. The importance of both is underscored by the complex viral-cell interactions that impact the lytic and latent states of the viral life cycle. These studies (i) have delineated functional domains of the protein; (ii) developed molecular models for HCF-1 domains; (iii) identified cellular and viral proteins that interact with various domains; (iii) elucidated a role for HCF-1 in the regulation of HSV DNA replication; (iv) characterized a unique mechanism for the regulation of protein-protein interactions via site-specific proteolytic processing; (v) demonstrated the biochemical mechanism involved in HCF-1 transcriptional coactivation; and (iv) identified HCF-1 as the essential component of both HSV and VZV viral IE gene expression.

单纯疱疹病毒裂解复制周期的起始取决于病毒（IE）立即基因的协调表达。 这些基因由由病毒和细胞成分组成的复杂多蛋白增强剂组件控制。 对各种成分，蛋白质相互作用，病毒和细胞功能的研究既是细胞转录调节的模型，又提供了对病毒所使用的机制的见解。 实验室的重点是对该法规途径的关键组成部分的识别和表征。 哺乳动物共激活因子HCF-1是增强子配合物和IE基因激活的更复杂因素之一。研究集中在病毒裂解周期以及正常细胞过程中的两个功能。 两者的重要性都受到影响病毒生命周期的裂解状态和潜在状态的复杂病毒细胞相互作用的强调。 这些研究（i）已经描绘了蛋白质的功能结构域。 （ii）开发了HCF-1结构域的分子模型； （iii）鉴定出与各种域相互作用的细胞和病毒蛋白； （iii）阐明了HCF-1在调节HSV DNA复制中的作用； （iv）表征了通过位点特异性蛋白水解加工调节蛋白质蛋白质相互作用的独特机制； （v）证明了HCF-1转录共激活涉及的生化机制； （iv）将HCF-1识别为HSV和VZV病毒IE基因表达的重要组成部分。