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Cited by 93Polyomavirus and related diseasesEpigenetics and DNA MethylationCancer-related gene regulation

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DNA Methyltransferase Is a Downstream Effector of Cellular Transformation Triggered by Simian Virus 40 Large T Antigen

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Slack, Andrew, Cervoni, Nadia, Pinard, Marc, Szyf, Moshe·1999·Journal of Biological Chemistry
DOI 10.1074/jbc.274.15.10105
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Abstract

This paper tests the hypothesis that DNA methyltransferase plays a causal role in cellular transformation induced by SV40 T antigen. We show that T antigen expression results in elevation of DNA methyltransferase (MeTase) mRNA, DNA MeTase protein levels, and global genomic DNA methylation. A T antigen mutant that has lost the ability to bind pRb does not induce DNA MeTase. This up-regulation of DNA MeTase by T antigen occurs mainly at the posttranscriptional level by altering mRNA stability. Inhibition of DNA MeTase by antisense oligonucleotide inhibitors results in inhibition of induction of cellular transformation by T antigen as determined by a transient transfection and soft agar assay. These results suggest that elevation of DNA MeTase is an essential component of the oncogenic program induced by T antigen.

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Metadata

Authors
Slack, A., Cervoni, N., Pinard, M., & Szyf, M.
Affiliations
McGill University (CA)
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1999-04
Volume
274
Issue
15
Pages
10105-10112
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.274.15.10105
OpenAlex
W2007287542
Cited by
93
References
1
Citations by year
2023: 5 · 2022: 1 · 2021: 2 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 5 · 2012: 2
FWCI
3.03
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Polyomavirus and related diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
Keywords
DNA methyltransferases, simian virus 40, T antigen, cell transformation, DNA methylation, mRNA stability, post-transcriptional regulation, carcinogenesis, soft agar colony formation
MeSH terms
Animals, Antigens, Viral, Tumor, Cell Transformation, Viral, Enzyme Induction, Mice, Inbred BALB C, Protein Processing, Post-Translational, RNA, Messenger, Simian virus 40, Transfection, DNA Modification Methylases, Up-Regulation, Oligonucleotides, Antisense, 3T3 Cells, DNA Methylation, Mice

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