DNA methyltransferase is a downstream effector of cellular transformation triggered by simian virus 40 large T antigen.
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.
Slack
A
A
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada.
Cervoni
N
N
Pinard
M
M
Szyf
M
M
D016475:3T3 Cells; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000235:genetics / Q000378:metabolism*; D002472:Cell Transformation, Viral; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D051379:Mice; D008807:Mice, Inbred BALB C; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D013539:Simian virus 40; D014162:Transfection; D015854:Up-Regulation
D000957:Antigens, Viral, Tumor; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D015254:DNA Modification Methylases