Related Experiment Video

Updated: Aug 15, 2026

Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
10:54

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

Published on: September 17, 2012

Calcineurin regulation of the mammalian G0/G1 checkpoint element, cyclin dependent kinase 4

S Baksh1, J A DeCaprio, S J Burakoff

  • 1Department of Pediatric Oncology, Dana Farber Cancer Institute, 44 Binney Street, Boston, Massachusetts, MA 02115, USA.

Oncogene
|June 13, 2000
PubMed

Insights

Calcineurin binding inhibits cyclin-dependent kinase 4 (cdk4) activity by dephosphorylation. This phosphatase activity is specific to cdk4, opposing the effects of cyclin-activating kinase complexes.

Area of Science:

  • Molecular Biology
  • Cell Cycle Regulation
  • Enzymology

Background:

  • Cyclin-dependent kinase 4 (cdk4) activity is regulated by subunit binding, phosphorylation, and calcium levels.
  • Understanding cdk4 regulation is crucial for comprehending cell cycle control in mammalian cells.

Purpose of the Study:

  • To investigate the interaction between cdk4 and calcineurin, a calcium-activated phosphatase.
  • To determine the effect of calcineurin activity on cdk4 kinase activity.

Main Methods:

  • Transient transfections in Jurkat cells to observe cdk4 and calcineurin binding.
  • Inhibition of calcineurin activity using FK506 and cyclosporin A.
  • In vitro phosphatase assays using calcineurin and cdk4.

Main Results:

  • Specific binding was observed between cdk4 and calcineurin.
  • Inhibition of calcineurin phosphatase activity increased cdk4 kinase activity, indicating an inhibitory role for calcineurin.
  • Calcineurin's inhibitory effect and dephosphorylation of cdk4 were specific to cdk4, not cdk6 or cdk2.

Conclusions:

  • Calcineurin directly dephosphorylates and inhibits cdk4 kinase activity.
  • Calcineurin acts antagonistically to cyclin-activating kinase complexes in regulating cdk4.
  • Calcineurin plays a significant role in the G0/G1 checkpoint control by modulating cdk4 activity.

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

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay12:26

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

Published on: May 3, 2018

Related Concept Videos

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 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...
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.
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...
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...
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...