Related Experiment Video

Updated: Jun 19, 2026

Analysis of Cell Cycle Position in Mammalian Cells
12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

Transcriptional downregulation of p27KIP1 through regulation of E2F function during LMP1-mediated transformation

David N Everly1, Bernardo A Mainou, Nancy Raab-Traub

  • 1Department of Microbiology and Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, USA. david.everly@rosalindfranklin.edu

Journal of Virology
|October 16, 2009
PubMed

Insights

Epstein-Barr virus LMP1 protein reduces p27 expression by decreasing its transcription, not affecting its protein levels. This mechanism involves E2F transcription factors and promotes cell cycle progression.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Virology

Background:

  • Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is a viral oncoprotein.
  • LMP1 induces fibroblast phenotypic transformation and alters cell cycle regulators.
  • Key affected regulators include p27 (cyclin-dependent kinase inhibitor), cyclin-dependent kinase 2, and retinoblastoma protein.

Purpose of the Study:

  • To investigate the effects of LMP1 on cell cycle progression.
  • To elucidate the mechanism by which LMP1 downregulates p27 expression.

Main Methods:

  • Analysis of p27 expression and activity in LMP1-expressing cells.
  • Reporter assays to assess p27 promoter activity.
  • Electrophoretic mobility shift assays (EMSA) to study transcription factor binding.

Main Results:

  • LMP1 did not affect ectopically expressed p27 protein levels.
  • LMP1 decreased p27 RNA levels and inhibited p27 promoter activity.
  • The LMP1-regulated promoter element was mapped to a region with E2F binding sites.
  • EMSA revealed binding of an inhibitory E2F complex (E2F4/p130) to the identified element.

Conclusions:

  • LMP1 decreases p27 transcription via modulation of E2F transcription factors.
  • This transcriptional downregulation of p27 contributes to LMP1-driven cell cycle stimulation.

More Related Videos

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

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.
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 daughter...
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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...