Related Experiment Video

Updated: Aug 9, 2026

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death
13:54

Preparation of Cell-lines for Conditional Knockdown of Gene Expression and Measurement of the Knockdown Effects on E4orf4-Induced Cell Death

Published on: October 21, 2012

Adenovirus E4orf4 protein binds to protein phosphatase 2A, and the complex down regulates E1A-enhanced junB

T Kleinberger1, T Shenk

  • 1Department of Molecular Biology, Howard Hughes Medical Institute, Princeton University, New Jersey 08544-1014.

Journal of Virology
|December 1, 1993
PubMed

Insights

Adenovirus E4orf4 protein binds protein phosphatase 2A, mediating the down regulation of junB transcription. This viral protein recruits the phosphatase into cellular signaling pathways involving cyclic AMP and E1A protein.

Area of Science:

  • Molecular biology
  • Virology
  • Cellular signaling

Background:

  • Adenovirus E4orf4 protein antagonizes junB transcription activated by cyclic AMP (cAMP) and E1A.
  • E4orf4 also induces hypophosphorylation of E1A and c-Fos proteins.

Purpose of the Study:

  • To investigate the mechanism by which adenovirus E4orf4 protein regulates junB transcription.
  • To identify the cellular interaction partners of E4orf4 involved in this process.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • In vitro phosphatase assays to measure enzymatic activity.
  • Analysis of junB gene transcription levels.

Main Results:

  • Adenovirus E4orf4 protein forms a stable complex with all three subunits of protein phosphatase 2A (PP2A).
  • The B subunit of PP2A directly interacts with the E4orf4 viral protein.
  • The E4orf4-PP2A complex exhibits PP2A-specific phosphatase activity.
  • This PP2A activity is responsible for the E4orf4-mediated downregulation of junB transcription.

Conclusions:

  • Adenovirus E4orf4 protein recruits PP2A into the cAMP and E1A-initiated signaling pathway.
  • PP2A is the key mediator of E4orf4's effect on junB transcription.
  • E4orf4 utilizes a host cell phosphatase to modulate viral and cellular gene expression.

More Related Videos

Isolation of Viral Replication Compartment-enriched Sub-nuclear Fractions from Adenovirus-infected Normal Human Cells10:22

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

Published on: November 12, 2015

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells08:47

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

Published on: May 1, 2020

Related Concept Videos

RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
Eukaryotic Transcription Activators02:42

Eukaryotic Transcription Activators

Transcription activators are proteins that promote the transcription of genes from DNA to RNA. In most cases, these proteins contain two separate domains ‒ a domain that binds to DNA and a domain for activating transcription; however, in some cases, a single domain is responsible for both binding and activation of transcription, as seen in the glucocorticoid receptor and MyoD.
The binding domains are capable of recognizing and interacting with regulatory sequences on the DNA. These domains are...
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a DNA...
Leaky Scanning02:28

Leaky Scanning

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...
RNA Polymerase II Accessory Proteins02:36

RNA Polymerase II Accessory Proteins

Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...