Latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts with RING3, a homolog of the Drosophila female sterile homeotic (fsh) gene

Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) is the likely infectio us cause of Kaposi's sarcoma, primary effusion lymphoma, and some cases of multicentric Castleman's disease. Its latent nuclear antigen (LANA) is expr essed in the nuclei of latently infected cells and may play a role in the p ersistence of episomal viral DNA in dividing cells. Here,ve report that LAN A interacts with RING3, a nuclear protein and member of the Drosophila fsh (female sterile homeotic) family of proteins, some of which have previously been implicated in controlling gene expression. Binding of RING3 to LANA i nvolves the ET domain, characteristic of fsh-related proteins, suggesting t hat this highly conserved region is involved in protein-protein interaction s. The interaction between RING3 and LANA results in phosphorylation of ser ine and threonine residues located between amino acids 951 and 1107 in the carboxy-terminal region of LANA. However, RING3 is not itself a kinase but appears to recruit an as yet unidentified serine/threonine protein kinase i nto the complex which it forms with LANA.