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Functional Imaging of Viral Transcription Factories Using 3D Fluorescence Microscopy
09:03

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Published on: January 18, 2018

Human polyomavirus BKV transcriptionally activates DNA methyltransferase 1 through the pRb/E2F pathway

M T McCabe1, J A Low, M J Imperiale

  • 1Program in Cellular and Molecular Biology, Department of Urology, University of Michigan, Ann Arbor, MI 48109-0944, USA.

Oncogene
|March 21, 2006
PubMed

Insights

Viral oncogenes activate DNA methyltransferase 1 (DNMT1) by targeting pocket proteins and E2F transcription factors. This DNMT1 activation may contribute to viral transformation and tumorigenesis.

Area of Science:

  • Molecular Biology
  • Virology
  • Oncology

Background:

  • DNA tumor viruses hijack host replication machinery via oncogenes targeting pocket proteins.
  • Pocket proteins regulate cell cycle and DNA synthesis by interacting with E2F transcription factors.
  • DNMT1 is an E2F target gene; its overexpression is linked to tumor suppressor gene hypermethylation and tumorigenesis.

Purpose of the Study:

  • To investigate if viral oncogenes activate DNMT1 expression.
  • To determine the role of pocket protein interaction and E2F sites in viral oncogene-mediated DNMT1 activation.
  • To explore the potential involvement of DNMT1 induction in viral transformation.

Main Methods:

  • Assessing DNMT1 activation by human polyomavirus BKV large T antigen (TAg) and adenovirus E1a.
  • Utilizing viral oncogene mutants defective in pocket protein binding.
  • Mutating E2F binding sites in the DNMT1 promoter to assess transcriptional activation.

Main Results:

  • DNMT1 is strongly activated by BKV TAg and adenovirus E1a.
  • Viral oncogene mutants unable to bind pocket proteins showed reduced DNMT1 activation.
  • Mutation of E2F sites in the DNMT1 promoter significantly impaired transcriptional activation.

Conclusions:

  • Viral oncogenes activate DNMT1 through the pRB/E2F pathway.
  • This viral induction of DNMT1 may play a role in virus-mediated cellular transformation.
  • Understanding this mechanism provides insights into oncogenesis by DNA tumor viruses.

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