TRIM25 RING-FINGER UBIQUITIN LIGASE RIG-I MEDIATED ANTI-VIRAL ROLE

TRIM25 环指泛素连接酶 RIG-I 介导的抗病毒作用

• 批准号: 7715510
• 负责人: Jae U Jung
• 金额: $ 3.24万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-05 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7715510
• 关键词: Acquired Immunodeficiency Syndrome; Boxing; C-terminal; Caspase; Cell Proliferation; Cell physiology; Coiled-Coil Domain; Computer Retrieval of Information on Scientific Projects Database; Estrogens; Fingers; Funding; Gene Targeting; Genes; Grant; Institution; Interferon Type I; Interferons; Link; Mediating; N-terminal; Natural Immunity; Production; Protein Family; Proteins; RNA; RNA Virus Infections; Reporting; Research; Research Personnel; Resources; Ring Finger Domain; Role; Signal Transduction; Source; TRIM Motif; Tretinoin; Ubiquitin; Ubiquitination; United States National Institutes of Health; Viral; Viral Physiology; Virus; Virus Diseases; human RBX1 protein; human TRIM25 protein; member; receptor; response; ubiquitin ligase; viral RNA

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Retinoic acid inducible gene-I (RIG-I) is a cytoplasmic RNA receptor that recognizes viral RNAs and initiates type I interferon (IFN)-mediated host protective innate immunity against viral infection. In addition, members of the tripartite motif (TRIM) protein family that contains a cluster of RING-finger domain, B-box/coiled-coil domain (B Box/CCD), and SPRY domain are involved in various cellular processes, including cell proliferation and anti-virus. Here, we report that the N-terminal caspase recruitment domains (CARDs) of RIG-I undergoes a robust ubiquitination induced by TRIM25 protein, also known as estrogen-responsive RING-finger protein (Efp). The C-terminal SPRY domain of TRIM25 interacts with the N-terminal CARD of RIG-I and this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARD of RIG-I, which consequently results in marked increase of RIG-I downstream signaling activity. RIG-I Lys-172 (K172) residue is critical for TRIM25-mediated ubiquitination as well as its ability to induce anti-viral signal transduction. Furthermore, gene targeting demonstrates that TRIM25 is essential not only for RIG-I ubiquitination but also for RIG-I mediated IFN-betta production and anti-viral activity in response to RNA virus infection. AIDS related.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 视黄酸诱导基因-I（RIG-I）是一种细胞质RNA受体，其识别病毒RNA并启动I型干扰素（IFN）介导的针对病毒感染的宿主保护性先天免疫。此外，包含一簇环指结构域、B盒/卷曲螺旋结构域（B Box/CCD）和SPRY结构域的三重基序（TRIM）蛋白家族的成员参与各种细胞过程，包括细胞增殖和抗病毒。在这里，我们报告说，N-末端caspase募集结构域（CARD）的RIG-I经历了一个强大的泛素化诱导的TRIM 25蛋白，也被称为雌激素响应环指蛋白（EFP）。TRIM 25的C-末端SPRY结构域与RIG-I的N-末端CARD相互作用，这种相互作用有效地将Lys 63连接的泛素部分递送到RIG-I的N-末端CARD，从而导致RIG-I下游信号传导活性的显著增加。RIG-I Lys-172（K172）残基对于TRIM 25介导的泛素化以及其诱导抗病毒信号转导的能力至关重要。此外，基因靶向证明TRIM 25不仅对于RIG-I泛素化是必需的，而且对于响应RNA病毒感染的RIG-I介导的IFN-β产生和抗病毒活性也是必需的。艾滋病相关