title: The Ebola virus VP24 protein prevents hnRNP C1/C2 binding to karyopherin α1 and partially alters its nuclear import.
abstract: The Ebola virus (EBOV) protein VP24 inhibits type I and II interferon (IFN) signaling by binding to NPI-1 subfamily karyopherin α (KPNA) nuclear import proteins, preventing their interaction with tyrosine-phosphorylated STAT1 (phospho-STAT1). This inhibits phospho-STAT1 nuclear import. A biochemical screen now identifies heterogeneous nuclear ribonuclear protein complex C1/C2 (hnRNP C1/C2) nuclear import as an additional target of VP24. Co-immunoprecipitation studies demonstrate that hnRNP C1/C2 interacts with multiple KPNA family members, including KPNA1. Interaction with hnRNP C1/C2 occurs through the same KPNA1 C-terminal region (amino acids 424-457) that binds VP24 and phospho-STAT1. The ability of hnRNP C1/C2 to bind KPNA1 is diminished in the presence of VP24, and cells transiently expressing VP24 redistribute hnRNP C1/C2 from the nucleus to the cytoplasm. These data further define the mechanism of hnRNP C1/C2 nuclear import and demonstrate that the impact of EBOV VP24 on nuclear import extends beyond STAT1.
authors: Mount Sinai School of Medicine, New York, New York 10029, USA.
authors: Reed S
authors: RS
authors: Shabman
authors: Erol E
authors: EE
authors: Gulcicek
authors: Kathryn L
authors: KL
authors: Stone
authors: Christopher F
authors: CF
authors: Basler
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D029043:Ebolavirus / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011817:Rabbits; D014709:Vero Cells; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism*; D028901:alpha Karyopherins / Q000235:genetics / Q000378:metabolism*
chemical_list: D034482:Heterogeneous-Nuclear Ribonucleoprotein Group C; C423142:KPNA1 protein, human; C446938:VP24 protein, Ebola virus; D014764:Viral Proteins; D028901:alpha Karyopherins