Hepatitis B Virus X Protein Activates Transcription by Bypassing CREB Phosphorylation, Not by Stabilizing bZIP−DNA Complexes

Although previous work has shown that the hepatitis B virus X protein (pX) stabilizes complexes between basic region leucine zipper (bZIP) proteins and target DNA, the relationship between enhanced binding and transcriptional activation has not been established. Here we show that interactions betwee...

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Bibliographic Details
Published in:Biochemistry (Easton) 2001-01, Vol.40 (3), p.693-703
Main Authors: Pflum, Mary Kay H, Schneider, Tanya L, Hall, David, Schepartz, Alanna
Format: Article
Language:English
Subjects:
Activating Transcription Factor 2
Animals
Basic-Leucine Zipper Transcription Factors
CREB protein
Cyclic AMP Response Element-Binding Protein - genetics
Cyclic AMP Response Element-Binding Protein - metabolism
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
G-Box Binding Factors
HeLa Cells
Hepatitis B virus
Hepatitis B virus - physiology
Humans
Phosphorylation
Promoter Regions, Genetic
Protein Binding - genetics
Rats
Response Elements
Trans-Activators - metabolism
Trans-Activators - physiology
Transcription Factor AP-1 - genetics
Transcription Factor AP-1 - metabolism
Transcription Factors - genetics
Transcription Factors - metabolism
Transcription, Genetic
Transcriptional Activation
X protein
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Summary:Although previous work has shown that the hepatitis B virus X protein (pX) stabilizes complexes between basic region leucine zipper (bZIP) proteins and target DNA, the relationship between enhanced binding and transcriptional activation has not been established. Here we show that interactions between CREB and pX, which coincidentally enhance DNA affinity, are necessary but not sufficient for increased transcriptional potency. Further, we show that transcriptional activation by pX requires a form of CREB in which Ser-133 is not phosphorylated. By stimulating the transcriptional potency of unphosphorylated CREB, pX can up-regulate the expression of cAMP-responsive genes implicated in hepatocyte proliferation, leading ultimately to the development of liver cancer after viral infection.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi0011936