Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

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.
Anaphase Promoting Complex00:50

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...
Anaphase Promoting Complex00:50

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...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Structure of cytoplasmic RNA polymerase II.

Nature communications·2026
Same author

Real-time visualization of reconstituted transcription reveals RNAPII activation mechanisms at single promoters.

Cell reports·2025
Same author

Ancestral Origin and Functional Expression of a Hyaluronic Acid Pathway Complement in Mussels.

Biology·2025
Same author

Multi-omics and biochemical reconstitution reveal CDK7-dependent mechanisms controlling RNA polymerase II function at gene 5'- and 3' ends.

Cell reports·2025
Same author

Regulation of RNA polymerase II transcription through re-initiation and bursting.

Molecular cell·2025
Same author

TF Profiler: a transcription factor inference method that broadly measures transcription factor activity and identifies mechanistically distinct networks.

Genome biology·2025

Related Experiment Video

Updated: Jun 25, 2026

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

The human CDK8 subcomplex is a molecular switch that controls Mediator coactivator function.

Matthew T Knuesel1, Krista D Meyer, Carrie Bernecky

  • 1Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA.

Genes & Development
|February 26, 2009
PubMed
Summary

The CDK8 subcomplex, not its kinase activity, uses Med12 and Med13 to repress gene transcription. This complex acts as a switch, controlling Mediator and RNA polymerase II interactions to regulate transcription initiation and reinitiation.

More Related Videos

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

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

Related Experiment Videos

Last Updated: Jun 25, 2026

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 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

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

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • Biochemistry

Background:

  • The human CDK8 subcomplex (CDK8, cyclin C, Med12, Med13) is known to negatively regulate transcription.
  • Previous research suggested CDK8 kinase activity was essential for this repressive function.

Purpose of the Study:

  • To elucidate the precise roles of CDK8 subcomplex components in transcriptional repression.
  • To investigate the mechanism by which the CDK8 subcomplex regulates transcription initiation and reinitiation.

Main Methods:

  • Utilized a reconstituted transcription system.
  • Employed recombinant and endogenous CDK8 subcomplexes.
  • Performed structural and biochemical studies.

Main Results:

  • Med12 and Med13, not CDK8 kinase activity, are critical for subcomplex-dependent repression.
  • The CDK8 subcomplex represses transcription reinitiation events, suggesting a role in fine-tuning transcript levels.
  • The CDK8 submodule binds the Mediator leg/tail domain via Med13, preventing pol II recruitment.

Conclusions:

  • The CDK8 subcomplex functions as a switch controlling Mediator-pol II interaction.
  • This mechanism regulates transcription initiation and reinitiation in human cells.
  • Repression of Mediator-pol II interaction may be a common mechanism for shutting down activated transcription.