Transactivating function and expression of the x gene of hepatitis B virus.

Abstract:

BACKGROUND/AIMS:The x gene of hepatitis B virus encodes a transactivating factor of 154 amino acids, termed HBx, which stimulates transcription of multiple viral and cellular genes. The transactivating function is probably associated with a tumorigenic potential of HBx, since x gene sequences, encoding functional HBx, have been repeatedly found integrated into the genome of liver carcinoma cells. METHODS:To identify the transactivating domain of HBx, we constructed x gene plasmids encoding full length HBx or HBx fragments. We determined their transactivating function after cotransfection of cells, along with a plasmid that contains a reporter gene driven by the SV40 early promoter/enhancer region. RESULTS:Our results demonstrate that a 95-amino acid fragment of HBx, encompassing amino acids 49 to 143, contains all the elements that are required for the transactivating function. Within this fragment a sequence element, encompassing amino acids 107 to 130, which contains a relatively high number of amino acids with charged side chains, appears to be crucial for the stimulation of gene expression. The influence of deletion mutations on x mRNA steady-state levels and HBx stability was examined. In essence, stable RNA and protein were produced if at least codons 1-82 or 70-154 were present in the deletion plasmids. CONCLUSION:This finding strongly suggests that the deletion of functional domains between codons 49 and 143, but not an instability of RNA and/or protein, was critical for the loss of transactivation.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Renner M,Haniel A,Bürgelt E,Hofschneider PH,Koch W

doi

10.1016/0168-8278(95)80311-4

subject

Has Abstract

pub_date

1995-07-01 00:00:00

pages

53-65

issue

1

eissn

0168-8278

issn

1600-0641

pii

0168-8278(95)80311-4

journal_volume

23

pub_type

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