Human polyomavirus BKV transcriptionally activates DNA methyltransferase 1 through the pRb/E2F pathway
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作者:
M T McCabe
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机构:Program in Cellular and Molecular Biology,Department of Urology
M T McCabe
J A Low
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h-index: 0
机构:Program in Cellular and Molecular Biology,Department of Urology
J A Low
M J Imperiale
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h-index: 0
机构:Program in Cellular and Molecular Biology,Department of Urology
M J Imperiale
M L Day
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机构:Program in Cellular and Molecular Biology,Department of Urology
M L Day
机构:
[1] Program in Cellular and Molecular Biology,Department of Urology
[2] University of Michigan,Department of Microbiology and Immunology
[3] University of Michigan,undefined
[4] University of Michigan,undefined
来源:
Oncogene
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2006年
/
25卷
关键词:
virus;
DNA methylation;
DNMT1;
E2F;
kidney;
D O I:
暂无
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学科分类号:
摘要:
Many DNA tumor virus oncogenes are capable of activating and highjacking the host cell's DNA replication machinery for its own reproduction purposes through targeting and inactivation of the retinoblastoma pocket protein family. Pocket proteins function to regulate cell cycle progression and DNA synthesis through inhibitory interactions with the E2F transcription factors. The interaction of viral oncogenes with the pocket proteins is crucial for their transforming activity. We recently demonstrated that the DNA methyltransferase 1 (DNMT1) gene is an E2F target gene that is transcriptionally activated in cells lacking the retinoblastoma gene (Rb−/−). Overexpression of DNMT1 is implicated in tumor suppressor gene hypermethylation which is associated with tumorigenesis. Given that viral oncogenes potently stimulate E2F activity, we hypothesized that viral infection might activate DNMT1 and thereby promote transformation. Herein, we demonstrate that DNMT1 is strongly activated by the human polyomavirus BKV large T antigen (TAg) and adenovirus E1a. Viral oncogene mutants incapable of binding the pocket proteins are ineffective at activating DNMT1 compared to their wild-type counterparts. Additionally, mutation of the E2F sites within the DNMT1 promoters dramatically abrogates transcriptional activation. These data suggest that viral induction of DNMT1 through modulation of the pRB/E2F pathway may be involved in viral transformation.
机构:
Cincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USACincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA
Hoskins, E. E.
Gunawardena, R. W.
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机构:
Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USACincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA
Gunawardena, R. W.
Habash, K. B.
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机构:
Cincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USACincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA
Habash, K. B.
Wise-Draper, T. M.
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机构:
Cincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USACincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA
Wise-Draper, T. M.
Jansen, M.
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机构:
Cincinnati Childrens Hosp, Med Ctr, Dept Pediat, Div Expt Hematol, Cincinnati, OH 45229 USACincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA
Jansen, M.
Knudsen, E. S.
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机构:
Thomas Jefferson Univ, Kimmel Canc Ctr, Dept Canc Biol, Philadelphia, PA 19107 USACincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA
Knudsen, E. S.
Wells, S. I.
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机构:
Cincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USACincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA
机构:
Univ Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, EnglandUniv Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, England
Barczak, Wojciech
Jin, Li
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机构:
Univ Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, EnglandUniv Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, England
Jin, Li
Carr, Simon Mark
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机构:
Univ Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, EnglandUniv Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, England
Carr, Simon Mark
Munro, Shonagh
论文数: 0引用数: 0
h-index: 0
机构:
Argonaut Therapeut Ltd, Magdalen Ctr, Oxford Sci Pk, Oxford OX4 4GA, EnglandUniv Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, England
Munro, Shonagh
Ward, Samuel
论文数: 0引用数: 0
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机构:
Argonaut Therapeut Ltd, Magdalen Ctr, Oxford Sci Pk, Oxford OX4 4GA, EnglandUniv Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, England
Ward, Samuel
Kanapin, Alexander
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机构:
St Petersburg State Univ, Ctr Genome Bioinformat, St Petersburg 199034, RussiaUniv Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, England
Kanapin, Alexander
Samsonova, Anastasia
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机构:
St Petersburg State Univ, Ctr Genome Bioinformat, St Petersburg 199034, RussiaUniv Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, England
Samsonova, Anastasia
La Thangue, Nicholas B.
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机构:
Univ Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, EnglandUniv Oxford, Dept Oncol, Lab Canc Biol, Old Rd,Campus Res Bldg, Oxford OX3 7DQ, England