Toxoplasma F-Box Protein Regulation of the Apicoplast

弓形虫 F-Box 蛋白对顶质体的调节

• 批准号: 10539694
• 负责人: Ira J Blader
• 金额: $ 23.99万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-23 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10539694
• 关键词: Affect; Architecture; Cell Cycle; Cell Nucleus; Cell physiology; Cells; Co-Immunoprecipitations; Complex; Cullin Proteins; Data; Daughter; Defect; Drug Targeting; Enzymes; Essential Genes; Euchromatin; Eukaryota; F Box Domain; F-Box Proteins; Family; Future; Gene Expression; Genome; Goals; Growth; Histone H3; Mediating; Membrane; Metabolic; Metabolism; Microscopy; Mitotic; Organelles; Parasites; Pathway interactions; Plasmodium; Plastids; Post-Translational Protein Processing; Protein Complex Subunit; Protein Subunits; Proteins; Proteome; Regulation; Resolution; Signal Transduction; Specificity; Structure; Testing; Toxoplasma; Toxoplasma gondii; Ubiquitination; Work; candidate identification; fitness; gene product; multicatalytic endopeptidase complex; novel; pathogen; protein degradation; recruit; trafficking; ubiquitin ligase; ubiquitin-protein ligase

The SKP1/Cullin/F-box (SCF) class of E3 Ubiquitin Ligases is an evolutionarily conserved family of enzymes that regulate key cellular processes including the cell cycle, membrane trafficking, and signaling. The SCF-E3 is composed of four core components - Rbx1, Cullin1, SKP1, and a F-box protein. F-box proteins are the subunits that recruit substrate proteins to be poly-ubiquitinated by the SCF-E3, and they can also be directly poly-ubiquitinated. In previous work, we discovered that the Toxoplasma genome contains 18 predicted F-box proteins and one of these, TgFBLX2, is predicted to be the most important for fitness. We now find that TgFBLX2 is indeed important for parasite growth and in its absence inheritance of the apicoplast, a relic plastid that serves as an important metabolic hub, is reduced. We further find that TgFBLX2 localizes to a unique perinucleolar compartment. The goal of this project is to define how TgFBLX2 mediates parasite growth. In the first aim, we will determine how TgFBLX2 regulates apicoplast inheritance. In the second aim, we will characterize the perinucleolar compartment in which TgFBLX2 resides. These studies are significant because they will reveal novel interactions between the nucleus and apicoplast. In addition, these findings may be relevant to related pathogens since TgFBLX2 is conserved in Plasmodium and other apicomplexans.

SKP1/Cullin/F-box （SCF）类E3泛素连接酶是一个进化上的