The Ubiquitin Ligase Itch and ESCRT Regulate EBV Nucleocapsid Egress from the Nuclear Envelope
Mei-Ru Chen1Guan-Ting Liu1Chung-Pei Lee Lee2Hsiu-Ni Kung3Lu-Ping Chow4Ling-Shih Chang Chang1Yu-Hsin Chang Chang1Chou-Wei Chang1
1. Graduate Institute and Department of Microbiology, College of Medicine, Taiwan University2. School of Nursing, Taipei University of Nursing and Health Sciences3. Department of Anatomy and Cell Biology, College of Medicine, Taiwan University4. Graduate Institute of Medical Genomics and Proteomics, College of Medicine, Taiwan University
摘要：The cellular endosomal sorting complex required for transport（ESCRT）was recently found to mediate important morphogenesis processes at the nuclear envelope（NE）.We previously showed that the Epstein-Barr virus（EBV）BFRF1 protein recruits the ESCRT-associated protein Alix to modulate NE structure and promote EBV nuclear egress.Here,we uncover new cellular factors and mechanisms involved in this process.BFRF1-induced NE vesicles are similar to those observed following EBV reactivation.BFRF1 is ubiquitinated and elimination of ubiquitination with either lysine mutations or fusion of a de-ubiquitinase hampers NE-derived vesicle formation and virus maturation.BFRF1 selectively binds the ubiquitin ligase Itch through a.a.181-313 sequence.Itch associates with an Alix-BFRF1 complex and is required for BFRF1-induced nucleocytoplasmic transport of EBV genomes.Our data demonstrate that Itch,ubiquitin and Alix control the BFRF1-mediated modulation of the NE and EBV maturation,uncovering novel regulatory mechanisms of ESCRT-induced nuclear egress of viral nucleocapsids.
2016 Membrane Shaping and Remodeling by Proteins（MSRP） Conference