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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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Related Experiment Video

Updated: May 19, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

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

Published on: May 3, 2018

CDK8 regulates E2F1 transcriptional activity through S375 phosphorylation.

J Zhao1, R Ramos, M Demma

  • 1Department of Late Stage Analytics, Merck, Sharpe, Dohme, Union, NJ, USA.

Oncogene
|September 5, 2012
PubMed
Summary

Cyclin-dependent kinase 8 (CDK8) promotes colorectal cancer by phosphorylating E2F1 at serine 375. This phosphorylation inactivates E2F1, impacting Wnt/β-catenin pathway activity in cancer development.

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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

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Related Experiment Videos

Last Updated: May 19, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

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

Published on: May 3, 2018

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
12:02

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

Published on: June 6, 2017

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Signaling

Background:

  • The Wnt/β-catenin pathway is crucial in colorectal cancer (CRC) development.
  • Cyclin-dependent kinase 8 (CDK8) is an oncogene amplified in many CRC tumors, mediating Wnt/β-catenin pathway activation.
  • CDK8 influences β-catenin activity through interactions with the mediator complex and by phosphorylating E2F1, a repressor of β-catenin/TCF transcription.

Purpose of the Study:

  • To identify the specific residue in E2F1 phosphorylated by CDK8.
  • To elucidate how this phosphorylation affects E2F1's transcriptional activity and its role in Wnt/β-catenin signaling.
  • To understand the mechanism by which CDK8 regulates E2F1's repressive function.

Main Methods:

  • In vitro kinase assays to determine CDK8 phosphorylation sites on E2F1.
  • Cellular experiments to confirm phosphorylation in vivo.
  • Analysis of E2F1-DNA binding and protein-protein interactions (CDK8, DP1).
  • Assessment of transcriptional activity of E2F1 on target genes.

Main Results:

  • CDK8 phosphorylates E2F1 at serine 375 (S375) both in vitro and in cells.
  • Phosphorylation of S375 is essential for E2F1 interaction with CDK8 and depends on CDK8 kinase activity.
  • CDK8-mediated phosphorylation of S375 inactivates E2F1's transcriptional activation function.
  • This regulation affects both repression of β-catenin/TCF-dependent genes and activation of E2F1-dependent genes.
  • E2F1 binding to DNA and interaction with DP1 remain unaffected.

Conclusions:

  • CDK8 directly phosphorylates E2F1 at S375, regulating its transcriptional activity.
  • This phosphorylation event is a key mechanism by which CDK8 influences the Wnt/β-catenin pathway in colorectal cancer.
  • Targeting the CDK8-E2F1 interaction or S375 phosphorylation may offer therapeutic strategies for CRC.