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Related Concept Videos

The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
The Spindle Assembly Checkpoint02:19

The Spindle Assembly Checkpoint

The spindle assembly checkpoint is a molecular surveillance mechanism ensuring the fidelity of chromosome segregation during anaphase. The checkpoint monitors the completion of all the prerequisite steps before chromosome segregation to determine whether the segregation process should proceed or be delayed.
Many proteins function together to control the spindle assembly checkpoint. Mutations affecting these proteins may allow cells to proceed into anaphase prematurely, resulting in the...
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.
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...
The Cell Cycle Control System02:11

The Cell Cycle Control System

The cell cycle is an organized set of events that leads the cell to divide into two daughter cells, each containing chromosomes identical to the parent cell. It is the cell cycle that leads to the formation of an entire organism from a single-cell zygote. Besides, cell division also functions in the renewal or repair of tissues in adult multicellular eukaryotes. For example, in the bone marrow, the stem cells divide to form new blood cells. Although essential for several functions, cell...
Inhibition of Cdk Activity02:34

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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...

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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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Published on: June 6, 2017

The mitotic checkpoint gene, SIL is regulated by E2F1.

Ayelet Erez1, Marie Chaussepied, Asher Castiel

  • 1Department of Pediatric Hemato-Oncology and the Sheba Cancer Research Center, Tel-Hashomer, Israel.

International Journal of Cancer
|July 24, 2008
PubMed
Summary

The E2F transcription factor regulates SIL gene expression, which is crucial for cell division and survival in cancer. This discovery offers potential new therapeutic strategies for treating cancers with high E2F activity.

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

Published on: May 1, 2020

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cell Cycle Regulation

Background:

  • SIL gene expression is elevated in various cancers, correlating with increased metastatic potential and mitotic spindle checkpoint genes.
  • SIL plays a role in mitotic entry, spindle organization, and cell survival.
  • E2F transcription factors are known regulators of cell cycle progression and have recently been implicated in controlling mitotic spindle checkpoint genes.

Purpose of the Study:

  • To investigate the hypothesis that E2F transcription factors regulate SIL gene expression.
  • To explore the functional relationship between E2F and SIL in cancer cells.

Main Methods:

  • Analysis of existing raw data from published experiments.
  • Experimental manipulation of E2F expression (overexpression and knockdown) in cell lines.
  • Reporter assays to assess promoter activity.
  • Chromatin immunoprecipitation (ChIP) to determine in vivo binding of E2F to the SIL promoter.

Main Results:

  • Ectopic expression or endogenous activation of E2F led to increased SIL expression.
  • Knockdown of E2F using shRNA resulted in downregulated SIL expression.
  • Reporter assays confirmed that E2F activates the SIL promoter.
  • Chromatin immunoprecipitation demonstrated that E2F binds to the SIL promoter in vivo.

Conclusions:

  • These findings establish that SIL is a direct transcriptional target of E2F.
  • E2F may regulate the G2/M cell cycle transition through the induction of SIL.
  • Targeting the SIL gene could be a relevant therapeutic strategy for cancers exhibiting constitutive E2F activation, as SIL silencing induces apoptosis in cancer cells.