Related Experiment Video

Updated: Apr 27, 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

18.3K

Cryo-EM structures of the CDK11-cyclin L-SAP30BP complex reveal mechanisms of CDK11 regulation

Amy J S McGeoch1, Victoria I Cushing1,2, Theodoros I Roumeliotis3

  • 1Division of Structural Biology, The Institute of Cancer Research, London, UK.

Nature Communications
|April 25, 2026
PubMed

Insights

We determined the structure of the CDK11-cyclin L-SAP30BP complex, crucial for mRNA splicing. This reveals how SAP30BP stabilizes cyclin L2 and promotes complex assembly, offering insights into CDK11 regulation and drug specificity.

Area of Science:

  • Molecular Biology
  • Structural Biology
  • Biochemistry

Background:

  • Cyclin-dependent kinase CDK11 plays vital roles in transcription, cell division, and mRNA splicing.
  • Activation of the spliceosome requires CDK11-mediated phosphorylation of SF3B1, a U2 snRNP component.

Purpose of the Study:

  • To elucidate the structural basis of spliceosome activation by the CDK11-cyclin L-SAP30BP complex.
  • To understand the regulatory mechanisms of CDK11 and the specificity of the inhibitor OTS964.

Main Methods:

  • Cryogenic electron microscopy (cryo-EM) at 2.3 Å resolution.
  • Biochemical experiments to analyze protein interactions and auto-regulation.
  • Structural comparison of inhibitor-bound complexes.

Main Results:

  • The structure reveals extensive interactions between SAP30BP and cyclin L2, stabilizing the complex.
  • SAP30BP critically interacts with CDK11's kinase lobe, facilitating complex assembly.
  • A pseudo-substrate sequence near the CDK11 C-terminus suggests a role in auto-regulation.
  • The structure of CDK11-cyclin L-SAP30BP bound to inhibitor OTS964 provides insights into its selectivity.

Conclusions:

  • SAP30BP is essential for stabilizing CDK11-cyclin L complexes and promoting spliceosome activation.
  • These findings illuminate CDK11 auto-regulation and the mechanism underlying OTS964 specificity.
  • The structural insights can guide the development of targeted therapeutics.

More Related Videos

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

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

10.9K
Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations10:54

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

Published on: September 17, 2012

10.3K

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...
4.8K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

4.3K
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.
5.3K
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.
100.8K
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

3.0K
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
4.7K