Related Experiment Video

Updated: Jul 14, 2026

Analysis of Cell Cycle Position in Mammalian Cells
12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes

Larisa Litovchick1, Subhashini Sadasivam, Laurence Florens

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.

Molecular Cell
|May 29, 2007
PubMed

Insights

Researchers discovered a conserved protein complex, DREAM, involving p130 and E2F4. This complex represses cell cycle genes during quiescence, offering new insights into gene regulation.

Area of Science:

  • Molecular Biology
  • Cell Cycle Regulation
  • Gene Expression

Background:

  • The Retinoblastoma (RB) protein family regulates gene expression, but its precise mechanisms, especially in quiescence, remain unclear.
  • RB-mediated repression involves E2F target genes and is conserved across species, with homologs in Drosophila and C. elegans.

Purpose of the Study:

  • To identify and characterize the mammalian protein complex responsible for RB-family-mediated repression of E2F target genes in quiescent cells.
  • To elucidate the composition and function of this complex in regulating cell cycle-dependent gene expression.

Main Methods:

  • Integrated proteomics, genomics, and bioinformatic analyses were employed.
  • Chromatin immunoprecipitation (ChIP) and mass spectrometry were used to identify protein interactions and DNA binding.
  • Analysis of protein complex dynamics during the cell cycle (G0 vs. S phase).

Main Results:

  • A novel p130-containing complex, termed DREAM (DP, RB-like, E2F, and MuvB), was identified, comprising mammalian homologs of C. elegans synMuvB proteins (LIN-9, LIN-37, LIN-52, LIN-54, LIN-53/RBBP4).
  • The DREAM complex binds to over 800 human promoters in the G0 (quiescent) phase and is essential for repressing E2F target genes.
  • During S phase, MuvB proteins dissociate from p130, form a distinct submodule, and bind to MYB, indicating dynamic regulation.

Conclusions:

  • The DREAM complex, containing p130 and E2F4 but not pRB, is an evolutionarily conserved regulator of cell cycle-dependent gene repression in quiescence.
  • This discovery provides a mechanistic link between RB family proteins, E2F, and MuvB homologs in controlling cell cycle exit and maintenance.
  • The findings offer new targets for understanding and potentially manipulating cell cycle control in various biological contexts.

More Related Videos

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Preparation of Primary Acute Lymphoblastic Leukemia Cells in Different Cell Cycle Phases by Centrifugal Elutriation09:09

Preparation of Primary Acute Lymphoblastic Leukemia Cells in Different Cell Cycle Phases by Centrifugal Elutriation

Published on: November 10, 2017

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.
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...
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...
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...