Hyperphosphorylation of EBNA2 by Epstein-Barr virus protein kinase suppresses transactivation of the LMP1 promoter.
The Epstein-Barr virus (EBV) BGLF4 gene encodes a serine/threonine protein kinase (PK) that is expressed in the cytolytic cycle. EBV nuclear antigen 2 (EBNA2) is a key latency gene essential for immortalization of B lymphocytes and transactivation of viral and cellular promoters. Here we report that EBV PK phosphorylates EBNA2 at Ser-243 and that these two proteins physically associate. PK suppresses EBNA2's ability to transactivate the LMP1 promoter, and Ser-243 of EBNA2 is involved in this suppression. Moreover, EBNA2 is hyperphosphorylated during EBV reactivation in latently infected B cells, which is associated with decreased LMP1 protein levels. This is the first report about the effect of EBV PK on the function of one of its target proteins and regulation of EBNA2 phosphorylation during the EBV lytic cycle.
Yue
Wei
W
Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Campus Box 7295, Chapel Hill, NC 27599, USA.
Gershburg
Edward
E
Pagano
Joseph S
JS
D015536:Down-Regulation; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism*; D006367:HeLa Cells / Q000821:virology; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012694:Serine; D015533:Transcriptional Activation; D014763:Viral Matrix Proteins / Q000235:genetics*; D014764:Viral Proteins / Q000378:metabolism*
C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D014763:Viral Matrix Proteins; D014764:Viral Proteins; D012694:Serine; C406063:BGLF4 protein, Epstein-Barr virus; D017346:Protein Serine-Threonine Kinases