A carboxy-terminal region of the hepatitis B virus X protein promotes DNA interaction of CREB and mimics the native protein for transactivation function.
Earlier we had shown that the conserved region E (residues 120-140) of HBV X protein (HBx) is crucial for transactivation. To investigate this region further, its oligomerisation was considered necessary to augment intracellular biochemical stability. Two to ten unit long tandem repeats of the E region (X16-n) were generated and their expression vectors constructed. Transient transfection of the E expression vectors along with different CAT constructs showed increase in the reporter activity. Interestingly a direct correlation was observed between the number of E repeat units in an expression vector and the level of transactivation. The transactivation levels with decameric X16 on different reporter constructs were comparable to those of the wild type HBx. Co-expression of X16 in a stable CHO-K1 cell line expressing the native HBx, showed co-operativity for transactivation. Further, X16 facilitated the binding of cAMP response element binding protein (CREB) to its responsive element just like the native HBx. The present study suggests that the C-terminal 'E' region of HBx represents its transactivation domain that acts by promoting the interaction of transcription factors to their cognate response elements.
Reddi
Honey
H
Virology Group, International Centre for Genetic Engineering and Biotechnology, P.O. Box 10504, Aruna Asaf Ali Marg, New Delhi 110067, India.
Kumar
Ravinder
R
Jain
Swatantra Kumar
SK
Kumar
Vijay
V
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D020080:Tandem Repeat Sequences / Q000235:genetics; D015534:Trans-Activators / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
D017362:Cyclic AMP Response Element-Binding Protein; D004279:DNA, Viral; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein