Human immunodeficiency virus-1(HIV-1)encodes simply 15 proteins and thus depends on multiple host cellular factors for virus reproduction.Spastin,a microtubule severing protein,is an identified HIV-1 dependency factor...Human immunodeficiency virus-1(HIV-1)encodes simply 15 proteins and thus depends on multiple host cellular factors for virus reproduction.Spastin,a microtubule severing protein,is an identified HIV-1 dependency factor,but the mechanism regulating HIV-1 is unclear.Here,the study showed that knockdown of spastin inhibited the production of the intracellular HIV-1 Gag protein and new virions through enhancing Gag lysosomal degradation.Further investigation showed that increased sodium tolerance 1(IST1),the subunit of endosomal sorting complex required for transport(ESCRT),could interact with the MIT domain of spastin to regulate the intracellular Gag production.In summary,spastin is required for HIV-1 replication,while spastin-IST1 interaction facilitates virus production by regulating HIV-1 Gag intracellular trafficking and degradation.Spastin may serve as new target for HIV-1 prophylactic and therapy.展开更多
带电多囊体蛋白5(charged multivesicular body protein 5,CHMP5)是一种高度保守的蛋白,其在酵母中的同源物是液泡蛋白分选相关蛋白60(vacuolar protein sorting-associated protein 60,Vps60)。作为内体分选转运复合体(endosomal sorti...带电多囊体蛋白5(charged multivesicular body protein 5,CHMP5)是一种高度保守的蛋白,其在酵母中的同源物是液泡蛋白分选相关蛋白60(vacuolar protein sorting-associated protein 60,Vps60)。作为内体分选转运复合体(endosomal sorting complex required for transport,ESCRT)III的重要一员,CHMP5参与细胞内蛋白降解、信号转导、病毒出芽等多种重要过程。CHMP5是一种抗凋亡基因,在急性髓系白血病等肿瘤、骨骼畸形的形成中发挥重要作用。此外,近年来的研究显示,CHMP5在T细胞分化、细胞分裂等过程中均有作用。展开更多
微自噬是真核生物体利用溶酶体直接降解蛋白质和受损细胞器的过程,在维持细胞稳态和生长发育中发挥重要作用。作为影响自噬流进程的关键复合物,内体分选转运复合体(endosomal sorting complex required for transport,ESCRT)和雷帕霉素...微自噬是真核生物体利用溶酶体直接降解蛋白质和受损细胞器的过程,在维持细胞稳态和生长发育中发挥重要作用。作为影响自噬流进程的关键复合物,内体分选转运复合体(endosomal sorting complex required for transport,ESCRT)和雷帕霉素靶蛋白复合体1(target of rapamycin complex 1,TORC1)在微自噬的调控通路中存在协同作用。本文通过系统性归纳并总结ESCRT与TORC1共同调控微自噬的分子机制,同时比较在不同类型的自噬中调控机制的差异,分析该领域仍存在的一些未解之谜,为发现调控自噬的新型分子机制提供可行性思路,为人类自噬相关疾病药物的研究提供潜在新靶点。展开更多
基金We greatly appreciate Prof.Charles Wood(University of Nebraska,Lincoln,USA)for the gift of the infectious molecular clones(pNL4.3,pNL4.3ΔEnvEGFP,and pVSV-G).the National Natural Science Foundation of China(81571987)Natural Science Foundation of Tianjin Municipal Science and Technology Commission(20JCQNJC01750,21JCQNJC01600).
文摘Human immunodeficiency virus-1(HIV-1)encodes simply 15 proteins and thus depends on multiple host cellular factors for virus reproduction.Spastin,a microtubule severing protein,is an identified HIV-1 dependency factor,but the mechanism regulating HIV-1 is unclear.Here,the study showed that knockdown of spastin inhibited the production of the intracellular HIV-1 Gag protein and new virions through enhancing Gag lysosomal degradation.Further investigation showed that increased sodium tolerance 1(IST1),the subunit of endosomal sorting complex required for transport(ESCRT),could interact with the MIT domain of spastin to regulate the intracellular Gag production.In summary,spastin is required for HIV-1 replication,while spastin-IST1 interaction facilitates virus production by regulating HIV-1 Gag intracellular trafficking and degradation.Spastin may serve as new target for HIV-1 prophylactic and therapy.
文摘带电多囊体蛋白5(charged multivesicular body protein 5,CHMP5)是一种高度保守的蛋白,其在酵母中的同源物是液泡蛋白分选相关蛋白60(vacuolar protein sorting-associated protein 60,Vps60)。作为内体分选转运复合体(endosomal sorting complex required for transport,ESCRT)III的重要一员,CHMP5参与细胞内蛋白降解、信号转导、病毒出芽等多种重要过程。CHMP5是一种抗凋亡基因,在急性髓系白血病等肿瘤、骨骼畸形的形成中发挥重要作用。此外,近年来的研究显示,CHMP5在T细胞分化、细胞分裂等过程中均有作用。
文摘微自噬是真核生物体利用溶酶体直接降解蛋白质和受损细胞器的过程,在维持细胞稳态和生长发育中发挥重要作用。作为影响自噬流进程的关键复合物,内体分选转运复合体(endosomal sorting complex required for transport,ESCRT)和雷帕霉素靶蛋白复合体1(target of rapamycin complex 1,TORC1)在微自噬的调控通路中存在协同作用。本文通过系统性归纳并总结ESCRT与TORC1共同调控微自噬的分子机制,同时比较在不同类型的自噬中调控机制的差异,分析该领域仍存在的一些未解之谜,为发现调控自噬的新型分子机制提供可行性思路,为人类自噬相关疾病药物的研究提供潜在新靶点。
