Identification of human cyclin-dependent kinase 8, a putative protein kinase partner for cyclin C

J P Tassan1, M Jaquenoud, P Léopold

  • 1Swiss Institute for Experimental Cancer Research (ISREC), Epalinges.

Insights

Researchers identified a human protein kinase, K35 (cyclin-dependent kinase 8 or CDK8), as a likely partner for cyclin C. This cyclin C-CDK8 complex may associate with the mammalian transcription apparatus, potentially relaying growth signals.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Metazoan cyclin C was initially identified for its role in rescuing yeast cell cycle deficiencies.
  • Understanding cyclin C's function was limited by the absence of its kinase partner.
  • Previous research suggested a potential role for cyclin C in cell cycle control.

Purpose of the Study:

  • To identify the physiological kinase partner of human cyclin C.
  • To investigate the interaction between cyclin C and its potential kinase partner.
  • To explore the functional association of the cyclin C-kinase complex in mammalian cells.

Main Methods:

  • In vitro translation of cyclin-dependent kinases (CDKs) and cyclins to demonstrate specific interactions.
  • Immunoprecipitation of K35 (CDK8) from HeLa cell extracts to detect associated cyclin C.
  • Structural and functional comparisons with the yeast SRB10-SRB11 CDK-cyclin pair.

Main Results:

  • A human protein kinase, K35 (CDK8), was identified as a likely physiological partner of cyclin C.
  • Specific in vitro interactions between K35 and cyclin C were demonstrated.
  • Cyclin C was detected in K35 immunoprecipitates from HeLa cells, confirming in vivo complex formation.
  • The K35-cyclin C complex shows structural similarity to the yeast SRB10-SRB11 complex.

Conclusions:

  • Human K35 (CDK8) and cyclin C form a complex in vivo.
  • This complex is structurally related to a component of the yeast RNA polymerase II holoenzyme.
  • The K35-cyclin C complex is proposed to be functionally associated with the mammalian transcription apparatus.
  • This association may play a role in relaying growth-regulatory signals.

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