GAMMAHV68 VMAP MITOCHONDRIAL ANTI-APOPTOSIS PROTEIN

GAMMAHV68 VMAP 线粒体抗凋亡蛋白

• 批准号: 7562107
• 负责人: Pinghui Feng
• 金额: $ 3.16万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7562107
• 关键词: Amphipathic Alpha Helix; Apoptosis; Apoptotic; Avidity; C-terminal; Cells; Computer Retrieval of Information on Scientific Projects Database; Funding; Gene Proteins; Grant; Herpesviridae; Institution; Mediating; Mitochondria; Mus; N-terminal; Normal Cell; Process; Proteins; Reporting; Research; Research Personnel; Resources; Simplexvirus; Source; United States National Institutes of Health; VDAC1 gene; Viral; Virus; Virus Diseases; cytochrome c; lytic replication; novel

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. Upon viral infection, cells undergo apoptosis as a defense against viral replication. Viruses, in turn, have evolved elaborate mechanisms to subvert apoptotic processes. Here, we report that a novel viral mitochondrial anti-apoptotic protein (vMAP) of murine gamma-herpesvirus 68 (gammaHV68) interacts with Bcl-2 and VDAC1 in a genetically and functionally separable manner. The N-terminal amphipathic alpha-helix region of vMAP interacted with Bcl-2 and this interaction markedly increased not only Bcl-2 recruitment to mitochondria but also its avidity for BH3-only proapoptotic proteins, thereby suppressing Bax mitochondrial translocation and activation. In addition, the central and C-terminal hydrophobic regions of vMAP interacted with VDAC1, resulting in effective inhibition of cytochrome c release. Consequently, these interactions induced the comprehensive inhibition of mitochondrion-mediated apoptosis. Finally, vMAP gene was required for efficient gammaHV68 lytic replication in normal cells, but not in mitochondrial apoptosis-deficient cells.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 病毒感染后，细胞会发生凋亡，以防御病毒复制。反过来，病毒进化出了复杂的机制来破坏细胞凋亡过程。在这里，我们报道了鼠伽马疱疹病毒 68 (gammaHV68) 的一种新型病毒线粒体抗凋亡蛋白 (vMAP) 以遗传和功能上可分离的方式与 Bcl-2 和 VDAC1 相互作用。 vMAP 的 N 端两亲性 α 螺旋区域与 Bcl-2 相互作用，这种相互作用不仅显着增加了 Bcl-2 向线粒体的募集，而且还显着增加了其对 BH3 促凋亡蛋白的亲和力，从而抑制了 Bax 线粒体易位和激活。此外，vMAP的中央和C端疏水区与VDAC1相互作用，从而有效抑制细胞色素c的释放。因此，这些相互作用诱导了线粒体介导的细胞凋亡的全面抑制。最后，在正常细胞中，vMAP 基因是有效的 gammaHV68 裂解性复制所必需的，但在线粒体凋亡缺陷的细胞中则不需要。