DNA Binding and Modulation of Gene Expression by the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus

doi:10.1128/JVI.75.17.7882-7892.2001

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Reprints and Permissions
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Garber, A. C.
	Articles by Renne, R.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Garber, A. C.
	Articles by Renne, R.

Previous Article | Next Article

Journal of Virology, September 2001, p. 7882-7892, Vol. 75, No. 17
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.17.7882-7892.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

DNA Binding and Modulation of Gene Expression by the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus

Alexander C. Garber, Marla A. Shu, Jianhong Hu, and Rolf Renne^*

Division of Hematology/Oncology and Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, Ohio 44106

Received 9 March 2001/Accepted 18 May 2001

Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with Kaposi's sarcoma, primary effusion lymphoma, and multicentricCastleman's disease. The latency-associated nuclear antigen (LANA)is highly expressed in these malignancies and has been shown toplay an important role in episomal maintenance, presumably bybinding to a putative oriP. In addition, LANA modulates cellularand viral gene expression and interacts with the cellular tumorsuppressors p53 and retinoblastoma suppressor protein. Many ofthese features are reminiscent of Epstein-Barr virus nuclear antigens(EBNAs), a family of six proteins expressed during latency. EBNA-1is required for episome maintenance, binds to oriP, and stronglyactivates transcription from two promoters, including its own.We have previously shown that LANA can transactivate its own promoterand therefore asked whether LANA, like EBNA-1, activates transcriptionby direct binding to DNA. By using recombinant LANA expressedfrom vaccinia virus vectors for electrophoretic mobility shiftassays, we found that LANA does not bind to its own promoter.In contrast, LANA binds specifically to sequences containing animperfect 20-bp palindrome in the terminal repeat (TR) of KSHV.We further show that the C-terminal domain of LANA is sufficientfor site-specific DNA binding. Unlike EBNA-1, which activatestranscription through binding of oriP, we found that LANA inhibitstranscription from a single TR binding site. A multimerized TRas found in the viral genome results in strong transcriptionalsuppression when linked to a heterologous promoter. These datasuggest that LANA, although fulfilling functions similar to thoseof EBNA-1, does so by very differentmechanisms.

^* Corresponding author. Mailing address: Division of Hematology/Oncology, Case Western Reserve University, Cleveland, OH 44106.Phone: (216) 368-1190. Fax: (216) 368-1166. E-mail: rfr3{at}po.cwru.edu.

This article has been cited by other articles:

Si, H., Verma, S. C., Lampson, M. A., Cai, Q., Robertson, E. S. (2008). Kaposi's Sarcoma-Associated Herpesvirus-Encoded LANA Can Interact with the Nuclear Mitotic Apparatus Protein To Regulate Genome Maintenance and Segregation. J. Virol. 82: 6734-6746 [Abstract] [Full Text]
Di Bartolo, D. L., Cannon, M., Liu, Y.-F., Renne, R., Chadburn, A., Boshoff, C., Cesarman, E. (2008). KSHV LANA inhibits TGF-{beta} signaling through epigenetic silencing of the TGF-{beta} type II receptor. Blood 111: 4731-4740 [Abstract] [Full Text]
Kelley-Clarke, B., Ballestas, M. E., Srinivasan, V., Barbera, A. J., Komatsu, T., Harris, T.-A., Kazanjian, M., Kaye, K. M. (2007). Determination of Kaposi's Sarcoma-Associated Herpesvirus C-Terminal Latency-Associated Nuclear Antigen Residues Mediating Chromosome Association and DNA Binding. J. Virol. 81: 4348-4356 [Abstract] [Full Text]
Adang, L. A., Parsons, C. H., Kedes, D. H. (2006). Asynchronous Progression through the Lytic Cascade and Variations in Intracellular Viral Loads Revealed by High-Throughput Single-Cell Analysis of Kaposi's Sarcoma-Associated Herpesvirus Infection.. J. Virol. 80: 10073-10082 [Abstract] [Full Text]
Murakami, Y., Yamagoe, S., Noguchi, K., Takebe, Y., Takahashi, N., Uehara, Y., Fukazawa, H. (2006). Ets-1-dependent Expression of Vascular Endothelial Growth Factor Receptors Is Activated by Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus through Interaction with Daxx. J. Biol. Chem. 281: 28113-28121 [Abstract] [Full Text]
You, J., Srinivasan, V., Denis, G. V., Harrington, W. J. Jr., Ballestas, M. E., Kaye, K. M., Howley, P. M. (2006). Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Interacts with Bromodomain Protein Brd4 on Host Mitotic Chromosomes.. J. Virol. 80: 8909-8919 [Abstract] [Full Text]
Si, H., Verma, S. C., Robertson, E. S. (2006). Proteomic Analysis of the Kaposi's Sarcoma-Associated Herpesvirus Terminal Repeat Element Binding Proteins.. J. Virol. 80: 9017-9030 [Abstract] [Full Text]
Cai, Q., Lan, K., Verma, S. C., Si, H., Lin, D., Robertson, E. S. (2006). Kaposi's Sarcoma-Associated Herpesvirus Latent Protein LANA Interacts with HIF-1{alpha} To Upregulate RTA Expression during Hypoxia: Latency Control under Low Oxygen Conditions.. J. Virol. 80: 7965-7975 [Abstract] [Full Text]
Lu, F., Day, L., Gao, S.-J., Lieberman, P. M. (2006). Acetylation of the Latency-Associated Nuclear Antigen Regulates Repression of Kaposi's Sarcoma-Associated Herpesvirus Lytic Transcription.. J. Virol. 80: 5273-5282 [Abstract] [Full Text]
Verma, S. C., Lan, K., Choudhuri, T., Robertson, E. S. (2006). Kaposi's Sarcoma-Associated Herpesvirus-Encoded Latency-Associated Nuclear Antigen Modulates K1 Expression through Its cis-Acting Elements within the Terminal Repeats.. J. Virol. 80: 3445-3458 [Abstract] [Full Text]
Verma, S. C., Choudhuri, T., Kaul, R., Robertson, E. S. (2006). Latency-Associated Nuclear Antigen (LANA) of Kaposi's Sarcoma-Associated Herpesvirus Interacts with Origin Recognition Complexes at the LANA Binding Sequence within the Terminal Repeats. J. Virol. 80: 2243-2256 [Abstract] [Full Text]
Henke-Gendo, C., Mengel, M., Hoeper, M. M., Alkharsah, K., Schulz, T. F. (2005). Absence of Kaposi's Sarcoma-associated Herpesvirus in Patients with Pulmonary Arterial Hypertension. Am. J. Respir. Crit. Care Med. 172: 1581-1585 [Abstract] [Full Text]
Viejo-Borbolla, A., Ottinger, M., Bruning, E., Burger, A., Konig, R., Kati, E., Sheldon, J. A., Schulz, T. F. (2005). Brd2/RING3 Interacts with a Chromatin-Binding Domain in the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 (LANA-1) That Is Required for Multiple Functions of LANA-1. J. Virol. 79: 13618-13629 [Abstract] [Full Text]
Wong, L.-Y., Wilson, A. C. (2005). Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Induces a Strong Bend on Binding to Terminal Repeat DNA. J. Virol. 79: 13829-13836 [Abstract] [Full Text]
Fujimuro, M., Liu, J., Zhu, J., Yokosawa, H., Hayward, S. D. (2005). Regulation of the Interaction between Glycogen Synthase Kinase 3 and the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen. J. Virol. 79: 10429-10441 [Abstract] [Full Text]
Dittmer, D. P., Gonzalez, C. M., Vahrson, W., DeWire, S. M., Hines-Boykin, R., Damania, B. (2005). Whole-Genome Transcription Profiling of Rhesus Monkey Rhadinovirus. J. Virol. 79: 8637-8650 [Abstract] [Full Text]
Lan, K., Kuppers, D. A., Verma, S. C., Sharma, N., Murakami, M., Robertson, E. S. (2005). Induction of Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen by the Lytic Transactivator RTA: a Novel Mechanism for Establishment of Latency. J. Virol. 79: 7453-7465 [Abstract] [Full Text]
Bechtel, J. T., Winant, R. C., Ganem, D. (2005). Host and Viral Proteins in the Virion of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 79: 4952-4964 [Abstract] [Full Text]
Lan, K., Kuppers, D. A., Robertson, E. S. (2005). Kaposi's Sarcoma-Associated Herpesvirus Reactivation Is Regulated by Interaction of Latency-Associated Nuclear Antigen with Recombination Signal Sequence-Binding Protein J{kappa}, the Major Downstream Effector of the Notch Signaling Pathway. J. Virol. 79: 3468-3478 [Abstract] [Full Text]
DeWire, S. M., Damania, B. (2005). The Latency-Associated Nuclear Antigen of Rhesus Monkey Rhadinovirus Inhibits Viral Replication through Repression of Orf50/Rta Transcriptional Activation. J. Virol. 79: 3127-3138 [Abstract] [Full Text]
Hu, J., Renne, R. (2005). Characterization of the Minimal Replicator of Kaposi's Sarcoma-Associated Herpesvirus Latent Origin. J. Virol. 79: 2637-2642 [Abstract] [Full Text]
An, F.-Q., Compitello, N., Horwitz, E., Sramkoski, M., Knudsen, E. S., Renne, R. (2005). The Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus Modulates Cellular Gene Expression and Protects Lymphoid Cells from p16 INK4A-induced Cell Cycle Arrest. J. Biol. Chem. 280: 3862-3874 [Abstract] [Full Text]
Srinivasan, V., Komatsu, T., Ballestas, M. E., Kaye, K. M. (2004). Definition of Sequence Requirements for Latency-Associated Nuclear Antigen 1 Binding to Kaposi's Sarcoma-Associated Herpesvirus DNA. J. Virol. 78: 14033-14038 [Abstract] [Full Text]
Stedman, W., Deng, Z., Lu, F., Lieberman, P. M. (2004). ORC, MCM, and Histone Hyperacetylation at the Kaposi's Sarcoma-Associated Herpesvirus Latent Replication Origin. J. Virol. 78: 12566-12575 [Abstract] [Full Text]
Ye, F.-C., Zhou, F.-C., Yoo, S. M., Xie, J.-P., Browning, P. J., Gao, S.-J. (2004). Disruption of Kaposi's Sarcoma-Associated Herpesvirus Latent Nuclear Antigen Leads to Abortive Episome Persistence. J. Virol. 78: 11121-11129 [Abstract] [Full Text]
Borah, S., Verma, S. C., Robertson, E. S. (2004). ORF73 of Herpesvirus Saimiri, a Viral Homolog of Kaposi's Sarcoma-Associated Herpesvirus, Modulates the Two Cellular Tumor Suppressor Proteins p53 and pRb. J. Virol. 78: 10336-10347 [Abstract] [Full Text]
Verma, S. C., Borah, S., Robertson, E. S. (2004). Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Up-Regulates Transcription of Human Telomerase Reverse Transcriptase Promoter through Interaction with Transcription Factor Sp1. J. Virol. 78: 10348-10359 [Abstract] [Full Text]
Wong, L.-Y., Matchett, G. A., Wilson, A. C. (2004). Transcriptional Activation by the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Is Facilitated by an N-Terminal Chromatin-Binding Motif. J. Virol. 78: 10074-10085 [Abstract] [Full Text]
Sakakibara, S., Ueda, K., Nishimura, K., Do, E., Ohsaki, E., Okuno, T., Yamanishi, K. (2004). Accumulation of Heterochromatin Components on the Terminal Repeat Sequence of Kaposi's Sarcoma-Associated Herpesvirus Mediated by the Latency-Associated Nuclear Antigen. J. Virol. 78: 7299-7310 [Abstract] [Full Text]
Lim, C., Choi, C., Choe, J. (2004). Mitotic Chromosome-Binding Activity of Latency-Associated Nuclear Antigen 1 Is Required for DNA Replication from Terminal Repeat Sequence of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 78: 7248-7256 [Abstract] [Full Text]
Lan, K., Kuppers, D. A., Verma, S. C., Robertson, E. S. (2004). Kaposi's Sarcoma-Associated Herpesvirus-Encoded Latency-Associated Nuclear Antigen Inhibits Lytic Replication by Targeting Rta: a Potential Mechanism for Virus-Mediated Control of Latency. J. Virol. 78: 6585-6594 [Abstract] [Full Text]
Canham, M., Talbot, S. J. (2004). A naturally occurring C-terminal truncated isoform of the latent nuclear antigen of Kaposi's sarcoma-associated herpesvirus does not associate with viral episomal DNA. J. Gen. Virol. 85: 1363-1369 [Abstract] [Full Text]
Jeong, J. H., Orvis, J., Kim, J. W., McMurtrey, C. P., Renne, R., Dittmer, D. P. (2004). Regulation and Autoregulation of the Promoter for the Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus. J. Biol. Chem. 279: 16822-16831 [Abstract] [Full Text]
Lim, C., Seo, T., Jung, J., Choe, J. (2004). Identification of a virus trans-acting regulatory element on the latent DNA replication of Kaposi's sarcoma-associated herpesvirus. J. Gen. Virol. 85: 843-855 [Abstract] [Full Text]
Abroi, A., Ilves, I., Kivi, S., Ustav, M. (2004). Analysis of Chromatin Attachment and Partitioning Functions of Bovine Papillomavirus Type 1 E2 Protein. J. Virol. 78: 2100-2113 [Abstract] [Full Text]
Barbera, A. J., Ballestas, M. E., Kaye, K. M. (2004). The Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 N Terminus Is Essential for Chromosome Association, DNA Replication, and Episome Persistence. J. Virol. 78: 294-301 [Abstract] [Full Text]
Fowler, P., Marques, S., Simas, J. P., Efstathiou, S. (2003). ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency. J. Gen. Virol. 84: 3405-3416 [Abstract] [Full Text]
Verma, S. C., Robertson, E. S. (2003). ORF73 of Herpesvirus Saimiri Strain C488 Tethers the Viral Genome to Metaphase Chromosomes and Binds to cis-Acting DNA Sequences in the Terminal Repeats. J. Virol. 77: 12494-12506 [Abstract] [Full Text]
Moorman, N. J., Willer, D. O., Speck, S. H. (2003). The Gammaherpesvirus 68 Latency-Associated Nuclear Antigen Homolog Is Critical for the Establishment of Splenic Latency. J. Virol. 77: 10295-10303 [Abstract] [Full Text]
Pan, H.-Y., Zhang, Y.-J., Wang, X.-P., Deng, J.-H., Zhou, F.-C., Gao, S.-J. (2003). Identification of a Novel Cellular Transcriptional Repressor Interacting with the Latent Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus. J. Virol. 77: 9758-9768 [Abstract] [Full Text]
Fujimuro, M., Hayward, S. D. (2003). The Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Manipulates the Activity of Glycogen Synthase Kinase-3{beta}. J. Virol. 77: 8019-8030 [Abstract] [Full Text]
Viejo-Borbolla, A., Kati, E., Sheldon, J. A., Nathan, K., Mattsson, K., Szekely, L., Schulz, T. F. (2003). A Domain in the C-Terminal Region of Latency-Associated Nuclear Antigen 1 of Kaposi's Sarcoma-Associated Herpesvirus Affects Transcriptional Activation and Binding to Nuclear Heterochromatin. J. Virol. 77: 7093-7100 [Abstract] [Full Text]
Dourmishev, L. A., Dourmishev, A. L., Palmeri, D., Schwartz, R. A., Lukac, D. M. (2003). Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis. Microbiol. Mol. Biol. Rev. 67: 175-212 [Abstract] [Full Text]
Fejer, G., Medveczky, M. M., Horvath, E., Lane, B., Chang, Y., Medveczky, P. G. (2003). The latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus interacts preferentially with the terminal repeats of the genome in vivo and this complex is sufficient for episomal DNA replication. J. Gen. Virol. 84: 1451-1462 [Abstract] [Full Text]
Watanabe, T., Sugaya, M., Atkins, A. M., Aquilino, E. A., Yang, A., Borris, D. L., Brady, J., Blauvelt, A. (2003). Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Prolongs the Life Span of Primary Human Umbilical Vein Endothelial Cells. J. Virol. 77: 6188-6196 [Abstract] [Full Text]
Schafer, A., Lengenfelder, D., Grillhosl, C., Wieser, C., Fleckenstein, B., Ensser, A. (2003). The Latency-Associated Nuclear Antigen Homolog of Herpesvirus Saimiri Inhibits Lytic Virus Replication. J. Virol. 77: 5911-5925 [Abstract] [Full Text]
Tang, J., Gordon, G. M., Muller, M. G., Dahiya, M., Foreman, K. E. (2003). Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Induces Expression of the Helix-Loop-Helix Protein Id-1 in Human Endothelial Cells. J. Virol. 77: 5975-5984 [Abstract] [Full Text]
Lim, C., Lee, D., Seo, T., Choi, C., Choe, J. (2003). Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus Functionally Interacts with Heterochromatin Protein 1. J. Biol. Chem. 278: 7397-7405 [Abstract] [Full Text]
Grundhoff, A., Ganem, D. (2003). The Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Permits Replication of Terminal Repeat-Containing Plasmids. J. Virol. 77: 2779-2783 [Abstract] [Full Text]
Shinohara, H., Fukushi, M., Higuchi, M., Oie, M., Hoshi, O., Ushiki, T., Hayashi, J.-I., Fujii, M. (2002). Chromosome Binding Site of Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Is Essential for Persistent Episome Maintenance and Is Functionally Replaced by Histone H1. J. Virol. 76: 12917-12924 [Abstract] [Full Text]
Krithivas, A., Fujimuro, M., Weidner, M., Young, D. B., Hayward, S. D. (2002). Protein Interactions Targeting the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus to Cell Chromosomes. J. Virol. 76: 11596-11604 [Abstract] [Full Text]
Hu, J., Garber, A. C., Renne, R. (2002). The Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Supports Latent DNA Replication in Dividing Cells. J. Virol. 76: 11677-11687 [Abstract] [Full Text]
Lim, C., Sohn, H., Lee, D., Gwack, Y., Choe, J. (2002). Functional Dissection of Latency-Associated Nuclear Antigen 1 of Kaposi's Sarcoma-Associated Herpesvirus Involved in Latent DNA Replication and Transcription of Terminal Repeats of the Viral Genome. J. Virol. 76: 10320-10331 [Abstract] [Full Text]
Garber, A. C., Hu, J., Renne, R. (2002). Latency-associated Nuclear Antigen (LANA) Cooperatively Binds to Two Sites within the Terminal Repeat, and Both Sites Contribute to the Ability of LANA to Suppress Transcription and to Facilitate DNA Replication. J. Biol. Chem. 277: 27401-27411 [Abstract] [Full Text]

J. Bacteriol.	Mol. Cell. Biol.	Microbiol. Mol. Biol. Rev.

Clin. Vaccine Immunol.	ALL ASM JOURNALS