Different regions of hepatitis B virus X protein are required for enhancement of bZip-mediated transactivation versus transrepression.
The hepatitis B virus X protein (pX) interacts directly with the bZip transactivator CREB and the bZip repressors ICERIIgamma and ATF3, increasing their DNA-binding affinity in vitro and their transcriptional efficacy in vivo. However, the mechanism of bZip-pX interaction and of the pX-mediated increase in the bZip transcriptional efficacy remains to be understood. In this study with deletion mutants of pX, we delineated a 67-amino-acid region spanning residues 49 to 115 required for direct CREB, ATF3, and ICER IIgamma interaction in vitro and in vivo and increased bZip/CRE binding in vitro. Transient transfections of the pX deletion mutants in AML12 hepatocytes demonstrate that pX(49-115) is as effective as the full-length pX in enhancing the ATF3- and ICERIIgamma-mediated transrepression. However, this pX region is inactive in increasing the transactivation efficacy of CREB; additional amino acid residues present in pX(49-140) are required to mediate the increased transactivation efficacy of CREB in vivo. This requirement for different regions of pX in affecting CREB transactivation suggests that amino acid residues 115 to 140 integrate additional events in effecting pX-mediated transactivation, such as concomitant interactions with select components of the basal transcriptional apparatus.
Barnabas
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Department of Basic Medical Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
Andrisani
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OM
D050976:Basic-Leucine Zipper Transcription Factors; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D051790:G-Box Binding Factors; D008099:Liver / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D012097:Repressor Proteins / Q000235:genetics*; D017384:Sequence Deletion; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics* / Q000502:physiology; 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