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Isolation of Viral Replication Compartment-enriched Sub-nuclear Fractions from Adenovirus-infected Normal Human Cells
10:22

Isolation of Viral Replication Compartment-enriched Sub-nuclear Fractions from Adenovirus-infected Normal Human Cells

Published on: November 12, 2015

The adenovirus E4-6/7 protein directs nuclear localization of E2F-4 via an arginine-rich motif

Joel E Schaley1, Marina Polonskaia, Patrick Hearing

  • 1Department of Molecular Genetics and Microbiology, School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA.

Journal of Virology
|February 1, 2005
PubMed

Insights

Adenovirus infection hijacks E2F transcription factors, crucial for cell regulation, by redirecting E2F-4 to the nucleus. This viral strategy enhances both viral and cellular gene expression during infection.

Area of Science:

  • Molecular Biology
  • Virology
  • Cell Biology

Background:

  • E2F transcription factors regulate cell proliferation, apoptosis, and differentiation.
  • Retinoblastoma protein (pRb) family members negatively regulate E2F activity.
  • Adenovirus (Ad) infection involves viral proteins that disrupt pRb-E2F interactions.

Purpose of the Study:

  • To investigate the role of adenovirus E4-6/7 protein in E2F regulation during infection.
  • To elucidate the mechanism of E2F-4 nuclear translocation induced by Ad E4-6/7.
  • To understand how Ad E4-6/7 protein contributes to the deregulation of host cell E2F function.

Main Methods:

  • Analysis of E2F transcription factor localization and activity in adenovirus-infected cells.
  • Investigating the interaction between adenovirus E4-6/7 protein and E2F-4.
  • Identifying the nuclear localization sequence within the E4-6/7 protein responsible for E2F-4 translocation.

Main Results:

  • Adenovirus E4-6/7 protein induces translocation of E2F-4 from the cytoplasm to the nucleus.
  • Nuclear E2F-4 becomes the predominant form of E2F DNA binding activity during Ad infection.
  • The N-terminal arginine-rich nuclear localization sequence of E4-6/7 is essential for E2F-4 nuclear import.
  • E4-6/7 cooperates with E1A oncoproteins to deregulate host E2F function.

Conclusions:

  • Adenovirus E4-6/7 protein actively manipulates host cell transcription factors by relocating E2F-4 to the nucleus.
  • This nuclear translocation of E2F-4 is critical for promoting viral gene expression and altering cellular processes.
  • The E4-6/7 protein's function in E2F deregulation is essential for the viral life cycle, involving both redundant and non-redundant mechanisms with E1A.

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