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Related Concept Videos

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...
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.
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.
M-Cdk Drives Transition Into Mitosis02:15

M-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...
M-Cdk Drives Transition Into Mitosis02:15

M-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...

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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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A Cdk7-Cdk4 T-loop phosphorylation cascade promotes G1 progression.

Miriam Merzel Schachter1, Karl A Merrick, Stéphane Larochelle

  • 1Department of Structural and Chemical Biology, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029-6574, USA.

Molecular Cell
|April 30, 2013
PubMed
Summary

The CDK-activating kinase Cdk7 activates Cdk4 and Cdk6 in human cells, maintaining their activity for cell cycle progression. This uncovers a CDK-activation cascade during G1 phase, potentially limiting passage through the restriction point.

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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Published on: May 3, 2018

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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Measuring Cell Cycle Progression Kinetics with Metabolic Labeling and Flow Cytometry
11:23

Measuring Cell Cycle Progression Kinetics with Metabolic Labeling and Flow Cytometry

Published on: May 22, 2012

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Eukaryotic cell division relies on cyclin-dependent kinases (CDKs) for regulation.
  • CDKs require phosphorylation by CDK-activating kinases (CAKs) for full activity.
  • Metazoan CAK Cdk7 is known to regulate Cdk2 and Cdk1 activity during S and G2 phases.

Purpose of the Study:

  • To investigate if Cdk7 also activates Cdk4 and Cdk6.
  • To determine the role of Cdk7 in G1 progression and restriction point passage.
  • To elucidate the regulation of Cdk4/Cdk6 activity by CDK-activating phosphorylation.

Main Methods:

  • Chemical genetics approaches were utilized.
  • Human cell lines were employed for experimentation.
  • In vitro kinase assays were performed.

Main Results:

  • Cdk7 was identified as a Cdk4- and Cdk6-activating kinase in human cells.
  • Cdk7 is required for maintaining Cdk4/Cdk6 activity, not just initial activation.
  • Cdk7 and Cdk4 activating phosphorylation increase concurrently as cells exit quiescence.
  • Cdk7 accelerates Cdk4 activation in vitro.

Conclusions:

  • Mitogen signaling initiates a CDK-activation cascade during G1 progression.
  • CAK activity, specifically Cdk7, may be rate-limiting for passing the restriction point.
  • This study reveals a novel role for Cdk7 in regulating G1 phase progression via Cdk4/Cdk6 activation.