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Related Concept Videos

Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
Mechanisms of Retrovirus-induced Cancers01:51

Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
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Mechanisms of Retrovirus-induced Cancers

Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
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During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
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Coronavirus

Coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV), are enveloped viruses characterized by their single-stranded, positive-sense RNA genome and helical nucleocapsid structure. The hallmark of these viruses is their club-shaped spike (S) glycoproteins that protrude from the viral envelope, facilitating attachment to host cells. Typically, coronaviruses infect the upper respiratory tract, often causing mild or asymptomatic disease. However, certain strains like...

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Adenovirus E1A directly targets the E2F/DP-1 complex.

Peter Pelka1, Matthew S Miller, Matthew Cecchini

  • 1Department of Pathology and Molecular Medicine, MG DeGroote Institute for Infectious Disease Research, McMaster University, MDCL 4077, 1280 Main Street West, Hamilton, ON, Canada L8S 4K1. peter.pelka@gmail.com

Journal of Virology
|July 1, 2011
PubMed
Summary

Adenovirus E1A 13S protein activates cell cycle gene expression independently of pRb binding. This novel mechanism involves direct E1A interaction with DP-1, enhancing E2F transcription factor activity during infection.

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Area of Science:

  • Molecular Biology
  • Virology
  • Cell Biology

Background:

  • Adenovirus infection requires cell cycle deregulation to propagate.
  • The pRb protein family controls cell cycle entry by repressing E2F transcription factors.
  • Viral E1A proteins typically activate E2F transcription and cell cycle entry via pRb interaction.

Purpose of the Study:

  • To investigate a novel mechanism of cell cycle deregulation by adenovirus E1A.
  • To determine if E1A can activate E2F-responsive genes independently of pRb family proteins.

Main Methods:

  • Investigated the interaction between adenovirus E1A 13S and E2F/DP-1 complexes.
  • Assessed E1A's ability to activate E2F-responsive gene expression.
  • Analyzed E2F4 occupancy at E2F-regulated promoters using E1A 13S and E1A 12S.

Main Results:

  • Adenovirus E1A 13S isoform activates E2F-responsive gene expression independently of pRb binding.
  • E1A directly binds to DP-1 within E2F/DP-1 complexes, recruiting E1A to promoters.
  • E1A 13S expression enhances E2F4 occupancy at E2F sites, unlike E1A 12S.

Conclusions:

  • Identified a novel mechanism of adenovirus-mediated cell cycle deregulation.
  • E1A 13S activates a subset of E2F-regulated genes through direct E2F/DP-1 interaction, independent of pRb.
  • This provides new insights into viral strategies for manipulating host cell machinery.