Al. Adamson et S. Kenney, The Epstein-Barr virus BZLF1 protein interacts physically and functionallywith the histone acetylase CREB-binding protein, J VIROLOGY, 73(8), 1999, pp. 6551-6558
The Epstein-Barr virus (EBV) immediate-early protein BZLF1 (Z) is a key reg
ulator of the EBV latent-to-lytic switch. Z is a transcriptional activator
which induces EBV early gene expression. We demonstrate here that Z interac
ts with CREB-binding protein (CBP), a histone acetylase and transcriptional
coactivator. This interaction requires the amino-terminal region of CBP as
well as the transactivation and leucine zipper domains of Z. We show that
CBP enhances Z-mediated transactivation of EBV early promoters, in reporter
gene assays and in the context of the endogenous genome. We also demonstra
te that Z decreases CREB transactivation function and that this inhibitory
effect is reversed by overexpression of CBP. We show that Z also interacts
directly with CREB. However, mutational analysis indicates that Z inhibitio
n of CREB activity requires the direct interaction between Z and CBP but no
t the direct interaction between Z and CREB. We propose that Z interacts wi
th CBP to enhance viral early gene transcription. In addition, the Z-CBP in
teraction may control host cellular transcription factor activity through c
ompetition for limiting amounts of cellular CBP.