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Science 10 May 1991:
Vol. 252. no. 5007, pp. 842 - 844
DOI: 10.1126/science.1827531
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Articles

Science, Vol 252, Issue 5007, 842-844
Copyright © 1991 by American Association for the Advancement of Science

articles

HBV X protein alters the DNA binding specificity of CREB and ATF-2 by protein-protein interactions

HF Maguire, JP Hoeffler, and A Siddiqui

Department of Microbiology and Immunology, University of Colorado School of Medicine, Denver 80262.

The hepatitis B virus (HBV) X gene product trans-activates viral and cellular genes. The X protein (pX) does not bind independently to nucleic acids. The data presented here demonstrate that pX entered into a protein-protein complex with the cellular transcriptional factors CREB and ATF-2 and altered their DNA binding specificities. Although CREB and ATF-2 alone did not bind to the HBV enhancer element, a pX-CREB or pX-ATF-2 complex did bind to the HBV enhancer. Thus, the ability of pX to interact with cellular factors broadened the DNA binding specificity of these regulatory proteins and provides a mechanism for pX to participate in transcriptional regulation. This strategy of altered binding specificity may modify the repertoire of genes that can be regulated by transcriptional factors during viral infection.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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COOH-Terminal Truncated HBV X Protein Plays Key Role in Hepatocarcinogenesis.
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The Hepatitis B Virus X Protein Functionally Interacts with CREB-binding Protein/p300 in the Regulation of CREB-mediated Transcription.
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Hepatitis B Virus X Protein Induces Perinuclear Mitochondrial Clustering in Microtubule- and Dynein-Dependent Manners.
S. Kim, H.-Y. Kim, S. Lee, S. W. Kim, S. Sohn, K. Kim, and H. Cho (2007)
J. Virol. 81, 1714-1726
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Hepatitis B Virus Promotes Angiopoietin-2 Expression in Liver Tissue: Role of HBV X Protein.
P. Sanz-Cameno, S. Martin-Vilchez, E. Lara-Pezzi, M. J. Borque, J. Salmeron, P. Munoz de Rueda, J. A. Solis, M. Lopez-Cabrera, and R. Moreno-Otero (2006)
Am. J. Pathol. 169, 1215-1222
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Activation of Focal Adhesion Kinase by Hepatitis B Virus HBx Protein: Multiple Functions in Viral Replication.
M. J. Bouchard, L. Wang, and R. J. Schneider (2006)
J. Virol. 80, 4406-4414
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Altered Proteolysis and Global Gene Expression in Hepatitis B Virus X Transgenic Mouse Liver.
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J. Virol. 80, 1405-1413
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Hepatitis B Virus X Protein Stimulates Viral Genome Replication via a DDB1-Dependent Pathway Distinct from That Leading to Cell Death.
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J. Virol. 79, 4238-4245
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The Enigmatic X Gene of Hepatitis B Virus.
M. J. Bouchard and R. J. Schneider (2004)
J. Virol. 78, 12725-12734
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Human Vaccinia-related Kinase 1 (VRK1) Activates the ATF2 Transcriptional Activity by Novel Phosphorylation on Thr-73 and Ser-62 and Cooperates with JNK.
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Inhibition of Cellular Proteasome Activities Enhances Hepadnavirus Replication in an HBX-Dependent Manner.
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Enhancer I Predominance in Hepatitis B Virus Gene Expression.
G. Doitsh and Y. Shaul (2004)
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Expression and function of chemokines during viral infections: from molecular mechanisms to in vivo function.
J. Melchjorsen, L. N. Sorensen, and S. R. Paludan (2003)
J. Leukoc. Biol. 74, 331-343
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Hepatitis B Virus X Protein Induces Cell Death by Causing Loss of Mitochondrial Membrane Potential.
Y. Shirakata and K. Koike (2003)
J. Biol. Chem. 278, 22071-22078
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Regulation of Hepatocyte Nuclear Factor 1 Activity by Wild-Type and Mutant Hepatitis B Virus X Proteins.
J. Li, Z. Xu, Y. Zheng, D. L. Johnson, and J.-h. Ou (2002)
J. Virol. 76, 5875-5881
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Functional characterization of the interferon regulatory element in the enhancer 1 region of the hepatitis B virus genome.
F. F. Alcantara, H. Tang, and A. McLachlan (2002)
Nucleic Acids Res. 30, 2068-2075
   Abstract »    Full Text »    PDF »
Hepatitis B Virus pX Interacts with HBXAP, a PHD Finger Protein to Coactivate Transcription.
M. Shamay, O. Barak, G. Doitsh, I. Ben-Dor, and Y. Shaul (2002)
J. Biol. Chem. 277, 9982-9988
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Enhancement of Hepatitis B Virus Replication by Its X Protein in Transgenic Mice.
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J. Virol. 76, 2579-2584
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J. Biol. Chem. 277, 8730-8740
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Calcium Signaling by HBx Protein in Hepatitis B Virus DNA Replication.
M. J. Bouchard, L.-H. Wang, and R. J. Schneider (2001)
Science 294, 2376-2378
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Mitochondrially Associated Hepatitis B Virus X Protein Constitutively Activates Transcription Factors STAT-3 and NF-kappa B via Oxidative Stress.
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Hepatitis B Virus HBx Protein Activation of Cyclin A-Cyclin-Dependent Kinase 2 Complexes and G1 Transit via a Src Kinase Pathway.
M. Bouchard, S. Giannakopoulos, E. H. Wang, N. Tanese, and R. J. Schneider (2001)
J. Virol. 75, 4247-4257
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Intracellular localization of the hepatitis B virus HBx protein.
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J. Gen. Virol. 82, 871-882
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Activation of NF-{kappa}B by hepatitis B virus X protein through an I{kappa}B kinase-independent mechanism.
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S. Y. Fuchs, I. Tappin, and Z.'e. Ronai (2000)
J. Biol. Chem. 275, 12560-12564
   Abstract »    Full Text »    PDF »
Viruses, Immunity, and Cancer: Lessons from Hepatitis B.
F. V. Chisari (2000)
Am. J. Pathol. 156, 1117-1132
   Full Text »    PDF »
Hepatitis B Virus X Protein Colocalizes to Mitochondria with a Human Voltage-Dependent Anion Channel, HVDAC3, and Alters Its Transmembrane Potential.
Z. Rahmani, K.-W. Huh, R. Lasher, and A. Siddiqui (2000)
J. Virol. 74, 2840-2846
   Abstract »    Full Text »
Hepatitis B Virus Biology.
C. Seeger and W. S. Mason (2000)
Microbiol. Mol. Biol. Rev. 64, 51-68
   Abstract »    Full Text »    PDF »
CREB Activation Induces Adipogenesis in 3T3-L1 Cells.
J. E. B. Reusch, L. A. Colton, and D. J. Klemm (2000)
Mol. Cell. Biol. 20, 1008-1020
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Different Regions of Hepatitis B Virus X Protein Are Required for Enhancement of bZip-Mediated Transactivation versus Transrepression.
S. Barnabas and O. M. Andrisani (2000)
J. Virol. 74, 83-90
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Hepatitis B Virus X Protein Is both a Substrate and a Potential Inhibitor of the Proteasome Complex.
Z. Hu, Z. Zhang, E. Doo, O. Coux, A. L. Goldberg, and T. J. Liang (1999)
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Ubiquitination and Degradation of ATF2 Are Dimerization Dependent.
S. Y. Fuchs and Z.'e. Ronai (1999)
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I. J. Groisman, R. Koshy, F. Henkler, J. D. Groopman, and M. A. Alaoui-Jamali (1999)
Carcinogenesis 20, 479-483
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Mechanism of Suppression of Hepatitis B Virus Precore RNA Transcription by a Frequent Double Mutation.
J. Li, V. E. Buckwold, M.-w. Hon, and J.-h. Ou (1999)
J. Virol. 73, 1239-1244
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Differential Immediate Early Gene Expression in Conditional Hepatitis B Virus pX-transforming Versus Nontransforming Hepatocyte Cell Lines.
C. Tarn, M. L. Bilodeau, R. L. Hullinger, and O. M. Andrisani (1999)
J. Biol. Chem. 274, 2327-2336
   Abstract »    Full Text »    PDF »
Regulation of RNA Polymerase I-Dependent Promoters by the Hepatitis B Virus X Protein via Activated Ras and TATA-Binding Protein.
H.-D. Wang, A. Trivedi, and D. L. Johnson (1998)
Mol. Cell. Biol. 18, 7086-7094
   Abstract »    Full Text »
The Hepatitis B Virus X Protein Is a Co-activator of Activated Transcription That Modulates the Transcription Machinery and Distal Binding Activators.
Y. Lin, H. Tang, T. Nomura, D. Dorjsuren, N. Hayashi, W. Wei, T. Ohta, R. Roeder, and S. Murakami (1998)
J. Biol. Chem. 273, 27097-27103
   Abstract »    Full Text »    PDF »
Liver-specific Enhancer II Is the Target for the p53-mediated Inhibition of Hepatitis B Viral Gene Expression.
H. Lee, H. T. Kim, and Y. Yun (1998)
J. Biol. Chem. 273, 19786-19791
   Abstract »    Full Text »    PDF »
The Human T-cell Leukemia Virus-1 Transcriptional Activator Tax Enhances cAMP-responsive Element-binding Protein (CREB) Binding Activity through Interactions with the DNA Minor Groove.
J. R. Lundblad, R. P. S. Kwok, M. E. Laurance, M. S. Huang, J. P. Richards, R. G. Brennan, and R. H. Goodman (1998)
J. Biol. Chem. 273, 19251-19259
   Abstract »    Full Text »    PDF »
Immune Pathogenesis of Hepatocellular Carcinoma.
Y. Nakamoto, L. G. Guidotti, C. V. Kuhlen, P. Fowler, and F. V. Chisari (1998)
J. Exp. Med. 188, 341-350
   Abstract »    Full Text »    PDF »
pX, the HBV-encoded coactivator, suppresses the phenotypes of TBP and TAFII250 mutants.
I. Haviv, Y. Matza, and Y. Shaul (1998)
Genes & Dev. 12, 1217-1226
   Abstract »    Full Text »
Cloning and Characterization of a Novel Hepatitis B Virus x Binding Protein That Inhibits Viral Replication.
M. Melegari, P. P. Scaglioni, and J. R. Wands (1998)
J. Virol. 72, 1737-1743
   Abstract »    Full Text »    PDF »
Hepatitis B Virus pX Targets TFIIB in Transcription Coactivation.
I. Haviv, M. Shamay, G. Doitsh, and Y. Shaul (1998)
Mol. Cell. Biol. 18, 1562-1569
   Abstract »    Full Text »
Hepatitis B Virus X Protein Interferes with Cellular DNA Repair.
S. A. Becker, T.-H. Lee, J. S. Butel, and B. L. Slagle (1998)
J. Virol. 72, 266-272
   Abstract »    Full Text »    PDF »
Hepatitis B virus X protein and p53 tumor suppressor interactions in the modulation of apoptosis.
L. W. Elmore, A. R. Hancock, S.-F. Chang, X. W. Wang, S. Chang, C. P. Callahan, D. A. Geller, H. Will, and C. C. Harris (1997)
PNAS 94, 14707-14712
   Abstract »    Full Text »    PDF »
The Hepatitis B Virus X Protein Enhances the DNA Binding Potential and Transcription Efficacy of bZip Transcription Factors.
S. Barnabas, T. Hai, and O. M. Andrisani (1997)
J. Biol. Chem. 272, 20684-20690
   Abstract »    Full Text »    PDF »
Hepatitis B virus HBx protein sensitizes cells to apoptotic killing by tumor necrosis factor alpha.
F. Su and R. J. Schneider (1997)
PNAS 94, 8744-8749
   Abstract »    Full Text »    PDF »
The hepatitis B virus X gene induces p53-mediated programmed cell death.
P. Chirillo, S. Pagano, G. Natoli, P. L. Puri, V. L. Burgio, C. Balsano, and M. Levrero (1997)
PNAS 94, 8162-8167
   Abstract »    Full Text »    PDF »
Activating Transcription Factor 2 (ATF2) Down-regulates Hepatitis B Virus X Promoter Activity by the Competition for the Activating Protein 1 Binding Site and the Formation of the ATF2-Jun Heterodimer.
C. Y. Choi, B. H. Choi, G. T. Park, and H. M. Rho (1997)
J. Biol. Chem. 272, 16934-16939
   Abstract »    Full Text »    PDF »
The Hepatitis B Virus X-associated Protein, XAP3, Is a Protein Kinase C-binding Protein.
Y.-S. Cong, Y.-L. Yao, W.-M. Yang, N. Kuzhandaivelu, and E. Seto (1997)
J. Biol. Chem. 272, 16482-16489
   Abstract »    Full Text »    PDF »
Hepatitis B Virus X Protein Is a Transcriptional Modulator That Communicates with Transcription Factor IIB and the RNA Polymerase II Subunit 5.
Y. Lin, T. Nomura, J. Cheong, D. Dorjsuren, K. Iida, and S. Murakami (1997)
J. Biol. Chem. 272, 7132-7139
   Abstract »    Full Text »    PDF »
Identification of the cAMP Response Element That Controls Transcriptional Activation of the Insulin-like Growth Factor-I Gene by Prostaglandin E2 in Osteoblasts.
M. J. Thomas, Y. Umayahara, H. Shu, M. Centrella, P. Rotwein, and T. L. McCarthy (1996)
J. Biol. Chem. 271, 21835-21841
   Abstract »    Full Text »    PDF »
Purification and Properties of Rat Liver Nuclear Proteins That Interact with the Hepatitis B Virus Enhancer 1.
M. J. Kosovsky, B. Huan, and A. Siddiqui (1996)
J. Biol. Chem. 271, 21859-21869
   Abstract »    Full Text »    PDF »
The Hepatitis B Virus Transactivator Protein, HBx, Interacts with Single-stranded DNA (ssDNA). BIOCHEMICAL CHARACTERIZATIONS OF THE HBx-ssDNA INTERACTIONS.
I. Qadri, M. E. Ferrari, and A. Siddiqui (1996)
J. Biol. Chem. 271, 15443-15450
   Abstract »    Full Text »    PDF »
Intramolecular inhibition of activating transcription factor-2 function by its DNA-binding domain..
X Y Li and M R Green (1996)
Genes & Dev. 10, 517-527
   Abstract »    PDF »
Transcription factor ATF2 regulation by the JNK signal transduction pathway.
S Gupta, D Campbell, B Derijard, and R. Davis (1995)
Science 267, 389-393
   Abstract »    PDF »
Platform Presentations.
(1993)
Toxicol Pathol 21, 611-623
   PDF »
Large Isoform of Hepatitis Delta Antigen Activates Serum Response Factor-associated Transcription.
T. Goto, N. Kato, S. K. Ono-Nita, H. Yoshida, M. Otsuka, Y. Shiratori, and M. Omata (2000)
J. Biol. Chem. 275, 37311-37316
   Abstract »    Full Text »    PDF »
The Hepatitis B Virus X Protein Induces HIV-1 Replication and Transcription in Synergy with T-cell Activation Signals. FUNCTIONAL ROLES OF NF-kappa B/NF-AT AND SP1-BINDING SITES IN THE HIV-1 LONG TERMINAL REPEAT PROMOTER.
M. Gomez-Gonzalo, M. Carretero, J. Rullas, E. Lara-Pezzi, J. Aramburu, B. Berkhout, J. Alcami, and M. Lopez-Cabrera (2001)
J. Biol. Chem. 276, 35435-35443
   Abstract »    Full Text »    PDF »
Hepatitis B Virus X Protein Differentially Activates RAS-RAF-MAPK and JNK Pathways in X-transforming Versus Non-transforming AML12 Hepatocytes.
C. Tarn, S. Lee, Y. Hu, C. Ashendel, and O. M. Andrisani (2001)
J. Biol. Chem. 276, 34671-34680
   Abstract »    Full Text »    PDF »
Structural and Functional Characterization of Interaction between Hepatitis B Virus X Protein and the Proteasome Complex.
Z. Zhang, N. Torii, A. Furusaka, N. Malayaman, Z. Hu, and T. J. Liang (2000)
J. Biol. Chem. 275, 15157-15165
   Abstract »    Full Text »    PDF »


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