(The) Kaposi's sarcoma-associated herpesvirus K8 protein binds to CREB-binding protein (CBP) and represses CBP-mediated transcription

Abstract

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is the eighth type of human herpesvirus (HHV8) and human gamma herpesvirus related to Epstein-Barr virus (EBV). KSHV has been implicated in the pathogenesis of Kaposi’s sarcoma and it encodes putative oncogenes and genes that may cause Kaposi’s sarcoma pathogenesis. KSHV open reading frame K8 encodes a protein of 237 amino acids with a prototypic basic region-leucine zipper (bZIP) domain at the carboxyl-terminus by in-frame splicing. KSHV K8 shows significant homology to the EBV immediate-early protein Zta, a key regulator in the reactivation and replication of EBV. In this study, we report that K8, like its homolog EBV Zta, interacts with cellular CREB-binding protein (CBP) in vivo and in vitro. This interaction requires the C/H3 domain of CBP and the basic region of K8. K8 represses CBP-mediated transcription by competing limited amounts of cellular CBP, exemplified by the reduced expression from the AP-1 and human immunodeficiency virus long terminal repeat promoters.