cdc2/cyclin B1-dependent phosphorylation of EBNA2 at Ser243 regulates its function in mitosis.
Epstein-Barr virus (EBV) nuclear antigen 2 (EBNA2) transactivates EBV genes in latently infected B cells. We have shown that mitotic hyperphosphorylation of EBNA2 suppresses its ability to transactivate the latent membrane protein 1 (LMP1) promoter. In this follow-up study, we identify EBNA2 Ser243 as a phosphorylation site for mitotic cdc2/cyclin B1 kinase. Mutation at Ser243, which mimics constitutive phosphorylation of the protein, decreases endogenous levels of both LMP1 and EBNA2. Moreover, mutation at Ser243 reduces the ability of EBNA2 to transactivate Cp, the promoter for all six EBV EBNA genes. Our data implicate EBNA2 Ser243 as a cdc2/cyclin B1 site of phosphorylation important for EBNA2's cotranscriptional function in mitosis.
Yue
Wei
W
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
Shackelford
Julia
J
Pagano
Joseph S
JS
D019943:Amino Acid Substitution; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism*; D056744:Cyclin B1; D019309:Epstein-Barr Virus Nuclear Antigens / Q000737:chemistry / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D010766:Phosphorylation; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D016415:Sequence Alignment; D012694:Serine / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014763:Viral Matrix Proteins / Q000032:analysis; D014764:Viral Proteins
C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D012333:RNA, Messenger; D012367:RNA, Viral; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D012694:Serine; D016203:CDC2 Protein Kinase