Related Experiment Video

Updated: Jul 14, 2026

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication
10:12

Measuring Endoplasmic Reticulum Stress and Unfolded Protein Response in HIV-1 Infected T-Cells and Analyzing its Role in HIV-1 Replication

Published on: June 14, 2024

HIV-1 Vpr activates the G2 checkpoint through manipulation of the ubiquitin proteasome system

Jason L DeHart1, Erik S Zimmerman, Orly Ardon

  • 1Division of Cell Biology and Immunology, Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT 84112, USA. jason.dehart@path.utah.edu

Virology Journal
|June 15, 2007
PubMed

Insights

The human immunodeficiency virus type 1 (HIV-1) Vpr protein requires the ubiquitin/proteasome system (UPS) to trigger G2 cell cycle arrest. Vpr interacts with DCAF1, a component of the C4a/DDB1 E3 ubiquitin ligase, which is essential for this process.

Area of Science:

  • Virology
  • Cell Biology
  • Molecular Biology

Background:

  • HIV-1 Vpr protein induces DNA replication stress, activating ATR and leading to G2 cell cycle arrest and apoptosis.
  • The ubiquitin/proteasome system (UPS) plays a critical role in regulating cellular processes, including cell cycle control.

Purpose of the Study:

  • To investigate the role of the UPS in HIV-1 Vpr-mediated G2 checkpoint activation.
  • To identify the specific E3 ubiquitin ligase subunits involved in Vpr's activity.

Main Methods:

  • Vpr-expressing cells were treated with proteasome inhibitors.
  • Vpr's interaction with E3 ubiquitin ligase subunits, specifically DCAF1, was analyzed using mutants.
  • The functional consequences of Vpr mutations on G2 arrest and dominant-negative effects were assessed.

Main Results:

  • The general function of the UPS is necessary for Vpr to induce G2 checkpoint activation, as proteasome inhibitors block this effect.
  • HIV-1 Vpr binds to the DCAF1 subunit of the cullin 4a/DDB1 E3 ubiquitin ligase.
  • Vpr interaction with DCAF1 is required but not sufficient for G2 arrest; specific mutations in Vpr affect its ability to bind DCAF1 and induce G2 arrest.

Conclusions:

  • The UPS is essential for HIV-1 Vpr to induce G2 arrest.
  • Vpr's interaction with DCAF1 is a critical step, but Vpr likely recruits an additional cellular factor for G2-to-M transition, leading to ubiquitination and degradation, thus preventing mitosis.

More Related Videos

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry09:38

Identification of Nucleolar Factors During HIV-1 Replication Through Rev Immunoprecipitation and Mass Spectrometry

Published on: June 26, 2019

Assaying Proteasomal Degradation in a Cell-free System in Plants07:43

Assaying Proteasomal Degradation in a Cell-free System in Plants

Published on: March 26, 2014

Related Concept Videos

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...
Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...