Related Experiment Video

Updated: Nov 19, 2025

Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
05:55

Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System

Published on: December 21, 2019

7.0K

Restoring the DREAM Complex Inhibits the Proliferation of High-Risk HPV Positive Human Cells

Claire D James1, Siddharth Saini2, Fatmata Sesay2

  • 1Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University (VCU), Richmond, VA 23298, USA.

Cancers
|January 30, 2021
PubMed

Insights

High-risk human papillomaviruses (HR-HPV) promote cancer by disrupting the DREAM complex. Restoring this complex in HR-HPV-positive cells inhibits proliferation, offering a potential therapeutic strategy for HPV-driven cancers.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • High-risk human papillomaviruses (HR-HPV) are linked to 5% of human cancers, including cervical, ano-genital, and head and neck carcinomas.
  • HR-HPV oncoproteins, particularly E7, target host tumor suppressors like retinoblastoma protein (pRb) and its relatives (p107, p130) to drive cancer progression.
  • The E7 protein's LxCxE motif binds RB proteins, disrupting cell-cycle control and the DREAM transcriptional repressor complex.

Purpose of the Study:

  • To investigate the role of DREAM complex disruption in HR-HPV-driven tumorigenesis.
  • To explore the therapeutic potential of restoring DREAM complex function in HR-HPV-positive cancers.

Main Methods:

  • Studied the interaction between the LIN52 adaptor protein within the DREAM complex and p130.
  • Engineered a LIN52 mutant (LIN52-S20C) with an altered motif to enhance binding to p130.
  • Assessed the impact of this mutation on DREAM complex assembly and cell proliferation in HPV-positive keratinocytes and cervical cancer cells.

Main Results:

  • LIN52 binds p130 via an E7-like LxSxE motif; altering this to LxCxE (LIN52-S20C) enhances p130 binding.
  • LIN52-S20C partially restored DREAM complex assembly in HR-HPV-positive cells.
  • Restoration of the DREAM complex led to inhibited proliferation in these cancer cells.

Conclusions:

  • Disruption of the DREAM complex by HR-HPV E7 is a key mechanism promoting cellular proliferation in HR-HPV-driven cancers.
  • Restoring the DREAM complex in HR-HPV-positive cells demonstrates therapeutic potential for treating associated cancers.
Keywords:
DREAME7cell cyclecervical cancerhead and neck cancerhuman papillomavirusoncogenic transformationprotein complextranscription

More Related Videos

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells09:04

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

Published on: March 7, 2025

1.0K
Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts10:04

Establishment of Proliferative Tetraploid Cells from Nontransformed Human Fibroblasts

Published on: January 8, 2017

7.5K

Related Concept Videos

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.
37.5K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.9K
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...
5.3K
DNA Damage can Stall the Cell Cycle02:37

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...
9.7K
DNA Damage Can Stall the Cell Cycle02:37

DNA Damage Can Stall the Cell Cycle

2.9K
Molecular Factors Affecting Cell Division01:27

Molecular Factors Affecting Cell Division

Several external and internal factors influence the initiation and inhibition of cell division. For instance, the death of nearby cells or the release of human growth hormone (hGH) promotes cell division. In contrast, lack of hGH or crowding of cells can inhibit cell division.
Several proteins function as internal regulators to ensure each cell cycle stage is completed faithfully before proceeding to the next. Regulator molecules may act directly or influence the activity or production of other...
3.6K