PLK1-dependent phosphorylation restrains EBNA2 activity and lymphomagenesis in EBV-infected mice

ABSTRACT: While Epstein-Barr virus (EBV) establishes a life-long latent infection in apparently healthy human immunocompetent hosts, immunodeficient individuals are at particular risk to develop lymphoproliferative B cell malignancies caused by EBV. A key EBV protein is the transcription factor EBV nuclear antigen 2 (EBNA2), which initiates B cell proliferation. Here, we combine biochemical, cellular and in vivo experiments demonstrating that the mitotic polo-like kinase 1 (PLK1) binds to EBNA2, phosphorylates its transactivation domain and thereby inhibits its biological activity. EBNA2 mutants that impair PLK1 binding or prevent EBNA2 phosphorylation are gain-of-function mutants. They exhibit enhanced transactivation capacities, accelerate the proliferation of infected B cells and promote the deve

SUBMITTER: Xiang Zhang 

PROVIDER: S-SCDT-EMBOR-2021-53007-T | biostudies-other |

REPOSITORIES: biostudies-other