C-Terminal Farnesylation of UCH-L1 Plays a Role in Transport of Epstein-Barr Virus Primary Oncoprotein LMP1 to Exosomes

• DOI: 10.1128/msphere.00030-18
• Publication Date: 2018-02-06T13:24:54Z
• Authors: E. Kobayashi; M. Aga; S. Kondo; C. Whitehurst; T. Yoshizaki; J. S. Pagano; J. Shackelford
• Keywords: Exosome

Increasing evidence shows that exosomes are key regulators in cancer cell-to-cell communication. Several reports on Epstein-Barr virus (EBV)-related malignancies demonstrate latent membrane protein 1 (LMP1) secreted by derived from EBV- or LMP1-positive cells can promote progression and metastasis. However, the mechanism which LMP1 is loaded into still poorly understood. Here, we examined whether process of loading linked to multifunctional molecule ubiquitin system-ubiquitin C-terminal hydrolase-L1 (UCH-L1). For first time, physically associated with UCH-L1 directing mediated farnesylation UCH-L1. Additionally, found FTI-277 farnesyltransferase inhibitor reduces motility- anchorage-independent growth EBV-positive functional assays. On basis our results, conclude one mechanisms sorted exosomes. We hypothesize inhibition specific small-molecule inhibitors blocks exosome-mediated transfer prometastatic molecules such as during communications thereby impedes invasion. IMPORTANCE Exosomes small vesicles secrete extracellular space, there increasing they have pivotal roles communication malignancy. It reported also EBV-associated malignant cells, including those nasopharyngeal carcinoma (NPC) B-cell lymphoma, These EBV-related may contain viral products contribute progression. The aim this study was investigate In study, show for time (UCH-L1) its farnesylation, a posttranslational lipid modification, mechanism. Our results suggest potential therapeutic target against metastasis