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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| Veröffentlicht in: | Biochemistry (Easton) 2001-01, Vol.40 (3), p.693-703 |
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| container_title | Biochemistry (Easton) |
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| creator | Pflum, Mary Kay H Schneider, Tanya L Hall, David Schepartz, Alanna |
| description | 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. |
| doi_str_mv | 10.1021/bi0011936 |
| format | Article |
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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. 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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.</description><subject>Activating Transcription Factor 2</subject><subject>Animals</subject><subject>Basic-Leucine Zipper Transcription Factors</subject><subject>CREB protein</subject><subject>Cyclic AMP Response Element-Binding Protein - genetics</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>G-Box Binding Factors</subject><subject>HeLa Cells</subject><subject>Hepatitis B virus</subject><subject>Hepatitis B virus - physiology</subject><subject>Humans</subject><subject>Phosphorylation</subject><subject>Promoter Regions, Genetic</subject><subject>Protein Binding - genetics</subject><subject>Rats</subject><subject>Response Elements</subject><subject>Trans-Activators - metabolism</subject><subject>Trans-Activators - physiology</subject><subject>Transcription Factor AP-1 - genetics</subject><subject>Transcription Factor AP-1 - metabolism</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transcription, Genetic</subject><subject>Transcriptional Activation</subject><subject>X protein</subject><issn>0006-2960</issn><issn>1520-4995</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0UFv0zAUB3ALgVi3ceALIF9AmkTYsx3HybHtNjapGhEtaOJiOY7DPNI42A5aOXDmzEfkk5Cq1bggcbKe_NP_Se-P0HMCbwhQclpZAEIKlj1CE8IpJGlR8MdoAgBZQosMDtBhCHfjmIJIn6IDQogAlmcT9OPS9CraaAOe4Y_WDwHf4NK7aGyHpzrabyqagFdedUF720frOlxt8GzTqxBs9xnP35_PcHnrQn_r_KZVW_EaX7u4ZcuoKtva71tYfboqf__8dXY9xXO37ltzb8IxetKoNphn-_cIfbg4X80vk8W7t1fz6SJRLIeY6KopCkIpzzUDnhY1zUEIYwhLNQXRcM0Z1KShJKekSCFjed2IOjNgcsF4w47Qq11u793XwYQo1zZo07aqM24IUkBGacrz_0IicjqmZyM82UHtXQjeNLL3dq38RhKQ21bkQyujfbEPHaq1qf_KfQ0jSHbAhmjuH_6V_yIzwQSXq3IpL2bLm5KzM7kY_cudVzrIOzf4bjzePxb_ARjNofs</recordid><startdate>20010123</startdate><enddate>20010123</enddate><creator>Pflum, Mary Kay H</creator><creator>Schneider, Tanya L</creator><creator>Hall, David</creator><creator>Schepartz, Alanna</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope><scope>7U9</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20010123</creationdate><title>Hepatitis B Virus X Protein Activates Transcription by Bypassing CREB Phosphorylation, Not by Stabilizing bZIP−DNA Complexes</title><author>Pflum, Mary Kay H ; Schneider, Tanya L ; Hall, David ; Schepartz, Alanna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a380t-cbf9912258c30549d28077ee134c207f5c530d1f21821940638df7d6e0e8735f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Activating Transcription Factor 2</topic><topic>Animals</topic><topic>Basic-Leucine Zipper Transcription Factors</topic><topic>CREB protein</topic><topic>Cyclic AMP Response Element-Binding Protein - genetics</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>G-Box Binding Factors</topic><topic>HeLa Cells</topic><topic>Hepatitis B virus</topic><topic>Hepatitis B virus - physiology</topic><topic>Humans</topic><topic>Phosphorylation</topic><topic>Promoter Regions, Genetic</topic><topic>Protein Binding - genetics</topic><topic>Rats</topic><topic>Response Elements</topic><topic>Trans-Activators - metabolism</topic><topic>Trans-Activators - physiology</topic><topic>Transcription Factor AP-1 - genetics</topic><topic>Transcription Factor AP-1 - metabolism</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Transcription, Genetic</topic><topic>Transcriptional Activation</topic><topic>X protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pflum, Mary Kay H</creatorcontrib><creatorcontrib>Schneider, Tanya L</creatorcontrib><creatorcontrib>Hall, David</creatorcontrib><creatorcontrib>Schepartz, Alanna</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biochemistry (Easton)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pflum, Mary Kay H</au><au>Schneider, Tanya L</au><au>Hall, David</au><au>Schepartz, Alanna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatitis B Virus X Protein Activates Transcription by Bypassing CREB Phosphorylation, Not by Stabilizing bZIP−DNA Complexes</atitle><jtitle>Biochemistry (Easton)</jtitle><addtitle>Biochemistry</addtitle><date>2001-01-23</date><risdate>2001</risdate><volume>40</volume><issue>3</issue><spage>693</spage><epage>703</epage><pages>693-703</pages><issn>0006-2960</issn><eissn>1520-4995</eissn><abstract>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. 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| source | MEDLINE; American Chemical Society Journals |
| 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 |
| title | Hepatitis B Virus X Protein Activates Transcription by Bypassing CREB Phosphorylation, Not by Stabilizing bZIP−DNA Complexes |
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