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Inhibition of Cdk Activity

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...

The Cell Cycle Control System

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...

Positive Regulator Molecules

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.

Negative Regulator Molecules

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.

Molecular Factors Affecting Cell Division

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...

Cells Coordinate Growth and Proliferation

Cells Coordinate Growth and Proliferation

Cell size is a significant factor impacting cellular design, function, and fitness. There exists some internal coordination by which cells double their masses before division, thus, achieving homeostasis. Coordination between cell growth and proliferation depends on the checkpoints in between cell cycle phases. Loss of coordination or failure in the checkpoint mechanism can drive the cell to uncontrolled growth and loss of cellular function. Like dividing cells that coordinate cellular growth,...

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Related Experiment Video

Updated: Jul 30, 2025

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

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Published on: June 6, 2017

Differential cell-cycle control by oscillatory versus sustained Hes1 expression via p21.

Yuki Maeda¹, Akihiro Isomura², Taimu Masaki³

¹RIKEN Center for Brain Science, Wako 351-0198, Japan; Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.

|May 18, 2023

Summary

Oscillatory Hes1 expression promotes neural stem cell (NSC) proliferation by down-regulating p21. Sustained Hes1, however, increases p21 and inhibits NSC proliferation through Erk signaling.

Keywords:

CP: Cell biology Hes1 neural stem cell oscillation p21 proliferation

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Area of Science:

Stem cell biology
Cell cycle regulation
Gene expression dynamics

Background:

Hes1 (Hairy and enhancer of split-related gene 1) plays a critical role in regulating neural stem cell (NSC) proliferation and quiescence.
The precise mechanisms by which Hes1's dynamic expression patterns influence cell proliferation remain incompletely understood.

Purpose of the Study:

To elucidate how Hes1's oscillatory versus sustained expression dynamics differentially control mouse neural stem cell (NSC) proliferation.
To investigate the molecular pathways, including p21 and Erk signaling, involved in Hes1-mediated cell cycle regulation.

Main Methods:

Analysis of Hes1 expression dynamics in mouse neural stem cells (NSCs).
Quantitative assessment of p21 (Cdkn1a) and Dusp7 expression levels.
Evaluation of phosphorylated Erk (p-Erk) signaling pathways.

Main Results:

Oscillatory Hes1 expression down-regulates p21, delaying cell-cycle progression and promoting NSC proliferation.
Sustained Hes1 overexpression up-regulates p21, inhibiting NSC proliferation, partly via repression of Dusp7 and subsequent increase in p-Erk.
Hes1 directly represses p21 during oscillation but indirectly up-regulates it during sustained expression.

Conclusions:

Hes1 differentially controls NSC proliferation based on its expression dynamics (oscillatory vs. sustained).
The p21 pathway is a key mediator of Hes1's opposing effects on NSC proliferation.
Understanding Hes1 dynamics offers insights into regulating neural stem cell fate and potential therapeutic strategies.