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Anaphase Promoting Complex

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...

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...

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...

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.

Positive Regulator Molecules

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.

Separation of Sister Chromatids

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...

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Related Experiment Video

Updated: May 10, 2026

Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations

Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations

Published on: September 17, 2012

Histone deacetylase 3 regulates cyclin A stability.

Miriam Vidal-Laliena¹, Edurne Gallastegui¹, Francesca Mateo²

¹From the Department of Cell Biology, Immunology and Neurosciences, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, 08036 Barcelona, Spain and.

The Journal of Biological Chemistry

|June 14, 2013

Summary

Histone deacetylase 3 (HDAC3) regulates cyclin A stability by deacetylating it, counteracting PCAF/GCN5 acetylation. HDAC3 degradation at mitosis facilitates cyclin A degradation, impacting cell cycle progression.

Keywords:

Cell Cycle Cyclin A Cyclins HDAC3 Histone Deacetylase PCAF Protein Degradation Protein Stability

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Last Updated: May 10, 2026

Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations

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Published on: September 17, 2012

Assays for Validating Histone Acetyltransferase Inhibitors

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Published on: August 6, 2020

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Area of Science:

Cell Biology
Molecular Biology
Biochemistry

Background:

Cyclin A acetylation by PCAF and GCN5 targets it for degradation during mitosis.
The precise mechanisms regulating cyclin A stability and its degradation pathway require further elucidation.

Purpose of the Study:

To investigate the role of histone deacetylase 3 (HDAC3) in regulating cyclin A stability.
To determine the interaction between HDAC3 and cyclin A and its functional consequences.

Main Methods:

Co-immunoprecipitation assays to confirm HDAC3-cyclin A interaction.
Western blotting to assess protein levels and acetylation status.
Proteasome inhibition assays.
Cell cycle analysis following HDAC3 knockdown.

Main Results:

HDAC3 directly interacts with and deacetylates cyclin A, particularly within the first 171 amino acids.
Overexpression of HDAC3 reduces cyclin A acetylation, while HDAC3 knockdown increases it.
Reduction of HDAC3 levels leads to decreased cyclin A levels, which is reversible by proteasome inhibitors.
HDAC3 itself is degraded via the proteasome during mitosis, promoting cyclin A acetylation and subsequent degradation.
HDAC3 knockdown disrupts cell cycle progression at both S phase and G2/M transition.

Conclusions:

HDAC3 acts as a key regulator of cyclin A stability by counteracting PCAF/GCN5-mediated acetylation.
HDAC3-mediated deacetylation and subsequent proteasomal degradation of HDAC3 at mitosis are crucial for timely cyclin A degradation and cell cycle progression.