Linked Life Data

10094970

Source:http://linkedlifedata.com/resource/pubmed/id/10094970

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-5-20
pubmed:abstractText
Natural occurring mutations in the preS-region are frequently found during chronic hepatitis B virus (HBV) infection. Here we used the mutated preS-region from a patient to study the transcriptional regulation of the S-promoter. The mutations were a CCAAT-box (MUT1) point mutation, a 6-base pair (bp) deletion (MUT2) 3' of the CCAAT-box, and a 153 bp deletion (MUT3) in the preS2 genome. Transfection experiments revealed for MUT1 and 2 30% to 40% and MUT3 75% of the wildtype (wt) S-promoter activity. In electro-mobility shift assays experiments, binding of a nuclear protein was impaired with MUT1. Ultraviolet cross-linking, South-Western, and gel shift experiments revealed a 30- to 40-kd protein interacting with the wt CCAAT-motif. Computer-assisted analysis and supershift experiments showed that CCAAT-binding factor (CBF) is the CCAAT-box binding protein. Cotransfection experiments with expression vectors for dominant-negative CBF or wt CBF showed that the wt S-promoter but not MUT1 could be regulated through CBF. Additionally, the CBF constructs did not modulate the basal activity of MUT2 but changes the activity of MUT3 like wt HBV. Artificial mutations were introduced in the MUT2 reporter constructs. Transfection experiments revealed that wt promoter activity could not be reconstituted. Therefore these experiments indicated the sterical position of CBF being essential for full S-promoter activity. Our study shows that the CCAAT-box and a second region is essential to mediate full S-promoter activity dependent on CBF. As these mutations also lead to retention of S-protein in the endoplasmic reticulum our results indicate that mutational changes in the preS-region might be linked to the progression of HBV-related liver disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1236-47
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Two control elements in the hepatitis B virus S-promoter are important for full promoter activity mediated by CCAAT-binding factor.
pubmed:affiliation
Department of Gastroenterology & Hepatology, Medizinische Hochschule, Hannover, Germany.
pubmed:publicationType
Journal Article