| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 30, 27401-27411, July 26, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Division of Hematology/Oncology, Department of Molecular
Biology and Microbiology, Case Western Reserve University,
Cleveland, Ohio 44106
The latency-associated nuclear antigen (LANA) of
Kaposi's sarcoma-associated herpesvirus is a multifunctional
protein with important roles in both transcriptional regulation and
episomal maintenance. LANA is also a DNA-binding protein and has been
shown to specifically bind to a region within the terminal repeat.
Here, we have performed a detailed analysis of the DNA-binding activity of LANA and show that it binds two sites separated by 22 bp. We used
electrophoretic mobility shift assay to quantitatively analyze the
binding sites and determined that the Kd of the
high affinity site is 1.51 ± 0.16 nM. Examination of
the contribution of nucleotides near the ends of the site showed that
the core binding site consists of 16 bp, 13 of which are conserved
between both sites. Analysis of the affinity of each site alone and in tandem revealed that the binding to the second site is primarily due to
cooperativity with the first site. Using deletion and point mutations,
we show that both sites contribute to the ability of LANA to suppress
transcription and to facilitate DNA replication. In addition, we show
that the ability of LANA to carry out these functions is directly
proportional to its affinity for the sites in this region. The
affinities, spacing, and cooperative binding between the two sites is
similar to that of the Epstein-Barr virus dyad symmetry element
oriP, suggesting a requirement for such an element in
latent replication of these related DNA tumor viruses.
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*
,
*
This work was supported in part by Grant CA 88763-2 from the
National Institutes of Health (to R. R.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Recipient of Research Oncology Training Grant T32 HL 07147 from
the National Institutes of Health.
§
Mount Sinai Healthcare Foundation Scholar. To whom correspondence
should be addressed: Div. of Hematology/Oncology, Dept. of Molecular
Biology and Microbiology, BRB R301, 2109 Adelbert Rd., Case Western
Reserve University, Cleveland, OH 44106. Tel.: 216-368-1190; Fax:
216-368-1166; E-mail: rfr3@po.cwru.edu.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Liu, H. J. Martin, G. Liao, and S. D. Hayward The Kaposi's Sarcoma-Associated Herpesvirus LANA Protein Stabilizes and Activates c-Myc J. Virol., October 1, 2007; 81(19): 10451 - 10459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. L. Skalsky, J. Hu, and R. Renne Analysis of Viral cis Elements Conferring Kaposi's Sarcoma-Associated Herpesvirus Episome Partitioning and Maintenance J. Virol., September 15, 2007; 81(18): 9825 - 9837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. J. Kwun, S. R. da Silva, I. M. Shah, N. Blake, P. S. Moore, and Y. Chang Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen 1 Mimics Epstein-Barr Virus EBNA1 Immune Evasion through Central Repeat Domain Effects on Protein Processing J. Virol., August 1, 2007; 81(15): 8225 - 8235. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. K. Nun, D. J. Kroll, N. H. Oberlies, D. D. Soejarto, R. J. Case, P. Piskaut, T. Matainaho, C. Hilscher, L. Wang, D. P. Dittmer, et al. Development of a fluorescence-based assay to screen antiviral drugs against Kaposi's sarcoma associated herpesvirus Mol. Cancer Ther., August 1, 2007; 6(8): 2360 - 2370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, H. Martin, M. Shamay, C. Woodard, Q.-Q. Tang, and S. D. Hayward Kaposi's Sarcoma-Associated Herpesvirus LANA Protein Downregulates Nuclear Glycogen Synthase Kinase 3 Activity and Consequently Blocks Differentiation J. Virol., May 1, 2007; 81(9): 4722 - 4731. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Kelley-Clarke, M. E. Ballestas, V. Srinivasan, A. J. Barbera, T. Komatsu, T.-A. Harris, M. Kazanjian, and K. M. Kaye Determination of Kaposi's Sarcoma-Associated Herpesvirus C-Terminal Latency-Associated Nuclear Antigen Residues Mediating Chromosome Association and DNA Binding J. Virol., April 15, 2007; 81(8): 4348 - 4356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Verma, T. Choudhuri, and E. S. Robertson The Minimal Replicator Element of the Kaposi's Sarcoma-Associated Herpesvirus Terminal Repeat Supports Replication in a Semiconservative and Cell-Cycle-Dependent Manner J. Virol., April 1, 2007; 81(7): 3402 - 3413. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, Q. Tang, G. G. Maul, and Y. Yuan Kaposi's Sarcoma-Associated Herpesvirus ori-Lyt-Dependent DNA Replication: Dual Role of Replication and Transcription Activator J. Virol., December 15, 2006; 80(24): 12171 - 12186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Verma, B. G. Bajaj, Q. Cai, H. Si, T. Seelhammer, and E. S. Robertson Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Recruits Uracil DNA Glycosylase 2 at the Terminal Repeats and Is Important for Latent Persistence of the Virus J. Virol., November 15, 2006; 80(22): 11178 - 11190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Shamay, A. Krithivas, J. Zhang, and S. D. Hayward Recruitment of the de novo DNA methyltransferase Dnmt3a by Kaposi's sarcoma-associated herpesvirus LANA PNAS, September 26, 2006; 103(39): 14554 - 14559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. You, V. Srinivasan, G. V. Denis, W. J. Harrington Jr., M. E. Ballestas, K. M. Kaye, and P. M. Howley Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Interacts with Bromodomain Protein Brd4 on Host Mitotic Chromosomes. J. Virol., September 1, 2006; 80(18): 8909 - 8919. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Si, S. C. Verma, and E. S. Robertson Proteomic Analysis of the Kaposi's Sarcoma-Associated Herpesvirus Terminal Repeat Element Binding Proteins. J. Virol., September 1, 2006; 80(18): 9017 - 9030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Lu, L. Day, S.-J. Gao, and P. M. Lieberman Acetylation of the Latency-Associated Nuclear Antigen Regulates Repression of Kaposi's Sarcoma-Associated Herpesvirus Lytic Transcription. J. Virol., June 1, 2006; 80(11): 5273 - 5282. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Verma, K. Lan, T. Choudhuri, and E. S. Robertson Kaposi's Sarcoma-Associated Herpesvirus-Encoded Latency-Associated Nuclear Antigen Modulates K1 Expression through Its cis-Acting Elements within the Terminal Repeats. J. Virol., April 1, 2006; 80(7): 3445 - 3458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Verma, T. Choudhuri, R. Kaul, and E. S. Robertson 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., March 1, 2006; 80(5): 2243 - 2256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Corte-Real, C. Collins, F. A. da Silva, J. P. Simas, C. F. Barbas III, Y. Chang, P. Moore, and J. Goncalves Intrabodies targeting the Kaposi sarcoma-associated herpesvirus latency antigen inhibit viral persistence in lymphoma cells Blood, December 1, 2005; 106(12): 3797 - 3802. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Viejo-Borbolla, M. Ottinger, E. Bruning, A. Burger, R. Konig, E. Kati, J. A. Sheldon, and T. F. Schulz 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., November 1, 2005; 79(21): 13618 - 13629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-Y. Wong and A. C. Wilson Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Induces a Strong Bend on Binding to Terminal Repeat DNA J. Virol., November 1, 2005; 79(21): 13829 - 13836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fujimuro, J. Liu, J. Zhu, H. Yokosawa, and S. D. Hayward Regulation of the Interaction between Glycogen Synthase Kinase 3 and the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen J. Virol., August 15, 2005; 79(16): 10429 - 10441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. M. Coleman, S. Efstathiou, and P. G. Stevenson Transcription of the murine gammaherpesvirus 68 ORF73 from promoters in the viral terminal repeats J. Gen. Virol., March 1, 2005; 86(3): 561 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hu and R. Renne Characterization of the Minimal Replicator of Kaposi's Sarcoma-Associated Herpesvirus Latent Origin J. Virol., February 15, 2005; 79(4): 2637 - 2642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Srinivasan, T. Komatsu, M. E. Ballestas, and K. M. Kaye Definition of Sequence Requirements for Latency-Associated Nuclear Antigen 1 Binding to Kaposi's Sarcoma-Associated Herpesvirus DNA J. Virol., December 15, 2004; 78(24): 14033 - 14038. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Stedman, Z. Deng, F. Lu, and P. M. Lieberman ORC, MCM, and Histone Hyperacetylation at the Kaposi's Sarcoma-Associated Herpesvirus Latent Replication Origin J. Virol., November 15, 2004; 78(22): 12566 - 12575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-C. Ye, F.-C. Zhou, S. M. Yoo, J.-P. Xie, P. J. Browning, and S.-J. Gao Disruption of Kaposi's Sarcoma-Associated Herpesvirus Latent Nuclear Antigen Leads to Abortive Episome Persistence J. Virol., October 15, 2004; 78(20): 11121 - 11129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-Y. Wong, G. A. Matchett, and A. C. Wilson Transcriptional Activation by the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Is Facilitated by an N-Terminal Chromatin-Binding Motif J. Virol., September 15, 2004; 78(18): 10074 - 10085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lim, C. Choi, and J. Choe 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., July 1, 2004; 78(13): 7248 - 7256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Canham and S. J. Talbot 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., June 1, 2004; 85(6): 1363 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Jeong, J. Orvis, J. W. Kim, C. P. McMurtrey, R. Renne, and D. P. Dittmer Regulation and Autoregulation of the Promoter for the Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus J. Biol. Chem., April 16, 2004; 279(16): 16822 - 16831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lim, T. Seo, J. Jung, and J. Choe Identification of a virus trans-acting regulatory element on the latent DNA replication of Kaposi's sarcoma-associated herpesvirus J. Gen. Virol., April 1, 2004; 85(4): 843 - 855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Gillet, F. Minner, B. Detry, F. Farnir, L. Willems, M. Lambot, E. Thiry, P.-P. Pastoret, F. Schynts, and A. Vanderplasschen Investigation of the Susceptibility of Human Cell Lines to Bovine Herpesvirus 4 Infection: Demonstration that Human Cells Can Support a Nonpermissive Persistent Infection Which Protects Them against Tumor Necrosis Factor Alpha-Induced Apoptosis J. Virol., March 1, 2004; 78(5): 2336 - 2347. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Barbera, M. E. Ballestas, and K. M. Kaye 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., January 1, 2004; 78(1): 294 - 301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. White, M. A. Calderwood, and A. Whitehouse Generation and precise modification of a herpesvirus saimiri bacterial artificial chromosome demonstrates that the terminal repeats are required for both virus production and episomal persistence J. Gen. Virol., December 1, 2003; 84(12): 3393 - 3403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Fowler, S. Marques, J. P. Simas, and S. Efstathiou ORF73 of murine herpesvirus-68 is critical for the establishment and maintenance of latency J. Gen. Virol., December 1, 2003; 84(12): 3405 - 3416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Verma and E. S. Robertson 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., December 1, 2003; 77(23): 12494 - 12506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H.-Y. Pan, Y.-J. Zhang, X.-P. Wang, J.-H. Deng, F.-C. Zhou, and S.-J. Gao Identification of a Novel Cellular Transcriptional Repressor Interacting with the Latent Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus J. Virol., September 15, 2003; 77(18): 9758 - 9768. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Viejo-Borbolla, E. Kati, J. A. Sheldon, K. Nathan, K. Mattsson, L. Szekely, and T. F. Schulz 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., June 15, 2003; 77(12): 7093 - 7100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Dourmishev, A. L. Dourmishev, D. Palmeri, R. A. Schwartz, and D. M. Lukac Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis Microbiol. Mol. Biol. Rev., June 1, 2003; 67(2): 175 - 212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Watanabe, M. Sugaya, A. M. Atkins, E. A. Aquilino, A. Yang, D. L. Borris, J. Brady, and A. Blauvelt Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Prolongs the Life Span of Primary Human Umbilical Vein Endothelial Cells J. Virol., June 1, 2003; 77(11): 6188 - 6196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lim, D. Lee, T. Seo, C. Choi, and J. Choe Latency-associated Nuclear Antigen of Kaposi's Sarcoma-associated Herpesvirus Functionally Interacts with Heterochromatin Protein 1 J. Biol. Chem., February 21, 2003; 278(9): 7397 - 7405. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Grundhoff and D. Ganem The Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Permits Replication of Terminal Repeat-Containing Plasmids J. Virol., February 15, 2003; 77(4): 2779 - 2783. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Krithivas, M. Fujimuro, M. Weidner, D. B. Young, and S. D. Hayward Protein Interactions Targeting the Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus to Cell Chromosomes J. Virol., October 11, 2002; 76(22): 11596 - 11604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hu, A. C. Garber, and R. Renne The Latency-Associated Nuclear Antigen of Kaposi's Sarcoma-Associated Herpesvirus Supports Latent DNA Replication in Dividing Cells J. Virol., October 11, 2002; 76(22): 11677 - 11687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Lim, H. Sohn, D. Lee, Y. Gwack, and J. Choe 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., September 11, 2002; 76(20): 10320 - 10331. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
