HBV X Protein Alters the DNA Binding Specificity of CREB and ATF-2 by Protein-Protein Interactions

TLDR

The HBV X protein trans‑activates viral and cellular genes yet lacks independent nucleic‑acid binding ability. pX forms complexes with CREB and ATF‑2, altering their DNA‑binding specificity so that the complexes bind the HBV enhancer and expand the repertoire of genes these transcription factors can regulate during infection.

Abstract

The hepatitis B virus (HBV) X gene product trans-activates viral and cellular genes. The X protein (pX) does not bind independently to nucleic acids. The data presented here demonstrate that pX entered into a protein-protein complex with the cellular transcriptional factors CREB and ATF-2 and altered their DNA binding specificities. Although CREB and ATF-2 alone did not bind to the HBV enhancer element, a pX-CREB or pX-ATF-2 complex did bind to the HBV enhancer. Thus, the ability of pX to interact with cellular factors broadened the DNA binding specificity of these regulatory proteins and provides a mechanism for pX to participate in transcriptional regulation. This strategy of altered binding specificity may modify the repertoire of genes that can be regulated by transcriptional factors during viral infection.