The hepatitis B virus X protein enhances the DNA binding potential and transcription efficacy of bZip transcription factors.
The hepatitis B virus X protein interacts with the basic-region, leucine zipper protein (bZip) domain of cAMP response element-binding protein increasing its affinity for the cAMP response element site in vitro and its transcriptional efficacy in vivo (Williams, J. S., and Andrisani, O. M. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 3819-3823). Here we examine pX interactions with bZip transcription factors ATF3, gadd153/Chop10, ICER IIgamma, and NF-IL6. We demonstrate direct interactions in vitro between pX and the bZip proteins tested. In contrast MyoD and Gal4(1-147) fail to interact with pX. We also demonstrate by the mammalian two-hybrid assay the direct interaction of pX with cAMP response element- binding protein, ICER IIgamma, ATF3, and NF-IL6 in hepatocytes. In addition, pX increases the DNA binding potential of bZip proteins for their cognate DNA-binding site in vitro. In transient transfections in hepatocytes (AML12 cell line), pX increases the transcriptional efficacy of the bZip transcription factors. NF-IL6-mediated transcriptional activation is enhanced 3-fold by pX. Most interestingly, pX augments the repression mediated by bZip repressors ATF3 and ICER IIgamma, by 6- and 7-fold, respectively, demonstrating for the first time the involvement of pX in gene repression. We conclude that pX is an enhancer of the DNA binding potential of bZip transcription factors, thereby increasing the transactivation or repression efficacy of bZip-responsive genes.
Barnabas
S
S
Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Hai
T
T
Andrisani
O M
OM
D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000502:physiology*; D051790:G-Box Binding Factors; D016350:Leucine Zippers; D012097:Repressor Proteins / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D054334:Viral Regulatory and Accessory Proteins
D050976:Basic-Leucine Zipper Transcription Factors; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051790:G-Box Binding Factors; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein; D004247:DNA