Related Experiment Video
Updated: Aug 9, 2026
12:26
Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
Cyclin D1-cdk4 induce runx2 ubiquitination and degradation
Run Shen1, Xiumei Wang, Hicham Drissi
1Department of Orthopaedics, Center for Musculoskeletal Research, University of Rochester School of Medicine, Rochester, NY 14642, USA.
The Journal of Biological Chemistry
|April 15, 2006
Summary
Cyclin D1-Cdk4 promote Runx2 degradation via ubiquitination, impacting bone cell regulation. Mutating Runx2 serine-472 blocks this, revealing a novel cell cycle control mechanism for Runx2 activity.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Runx2 is a key transcription factor for osteoblast and chondrocyte gene activation.
- Runx2 activity is controlled by transcriptional and post-transcriptional mechanisms.
- The role of Runx2 post-translational modifications remains incompletely understood.
Purpose of the Study:
- To investigate the functional significance of Runx2 post-translational modifications.
- To elucidate the mechanism by which cell cycle regulators affect Runx2 stability.
Main Methods:
- Ubiquitination and proteasome assays were used to study Runx2 degradation.
- Site-directed mutagenesis of Runx2 at serine-472 was performed.
- Analysis of Runx2 half-life and sensitivity to cyclin D1-induced degradation.
Main Results:
- Cyclin D1-Cdk4 complex induces Runx2 degradation through the ubiquitination-proteasome pathway.
- Mutation of Runx2 serine-472 to alanine enhances its half-life.
- The S472A mutation renders Runx2 resistant to cyclin D1-mediated degradation.
Conclusions:
- Cyclin D1-Cdk4-mediated Runx2 degradation represents a novel regulatory mechanism.
- Runx2 activity is coordinately regulated with the cell cycle machinery in bone cells.
- Post-translational modification of Runx2 plays a critical role in bone cell differentiation and function.
Related Concept Videos
02:34Inhibition 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...
02:34Inhibition 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...
00:50Anaphase 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...
02:39Positive 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.
01:45Positive Regulator Molecules
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
02:15M-Cdk Drives Transition Into Mitosis
Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...