title: Regulation of Latent Membrane Protein 1 Signaling through Interaction with Cytoskeletal Proteins.
abstract: Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) induces constitutive signaling in EBV-infected cells to ensure the survival of the latently infected cells. LMP1 is localized to lipid raft domains to induce signaling. In the present study, a genome-wide screen based on bimolecular fluorescence complementation (BiFC) was performed to identify LMP1-binding proteins. Several actin cytoskeleton-associated proteins were identified in the screen. Overexpression of these proteins affected LMP1-induced signaling. BiFC between the identified proteins and LMP1 was localized to lipid raft domains and was dependent on LMP1-induced signaling. Proximity biotinylation assays with LMP1 induced biotinylation of the actin-associated proteins, which were shifted in molecular mass. Together, the findings of this study suggest that the association of LMP1 with lipid rafts is mediated at least in part through interactions with the actin cytoskeleton.
  
  
  OBJECTIVE
  LMP1 signaling requires oligomerization, lipid raft partitioning, and binding to cellular adaptors. The current study utilized a genome-wide screen to identify several actin-associated proteins as candidate LMP1-binding proteins. The interaction between LMP1 and these proteins was localized to lipid rafts and dependent on LMP1 signaling. This suggests that the association of LMP1 with lipid rafts is mediated through interactions with actin-associated proteins.
authors.affiliation: Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Holthusen
authors.affiliation: Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA.
authors.forename: Pooja
authors.initials: P
authors.lastname: Talaty
authors.affiliation: Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, Illinois, USA david.everly@rosalindfranklin.edu.
authors.forename: David N
authors.initials: DN
authors.lastname: Everly
mesh_terms: D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D011485:Protein Binding; D015398:Signal Transduction; D014763:Viral Matrix Proteins / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins