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Updated: Oct 25, 2025
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Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
Published on: February 25, 2016
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Functional characterization of CDK10 and cyclin M truncated variants causing severe developmental disorders
Thomas Robert1, Anne-Catherine Dock-Bregeon1, Pierre Colas1
1Laboratory of Integrative Biology of Marine Models, Station Biologique de Roscoff, Sorbonne Université/CNRS, Roscoff, France.
Molecular Genetics & Genomic Medicine
|August 9, 2021
Summary
Truncated CDK10 and CycM variants retain heterodimerization but lose kinase activity, leading to Al Kaissi and STAR syndromes due to proteasomal degradation and reduced CDK10/CycM function.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Cyclin M (CycM)-dependent kinase CDK10 is poorly understood.
- Loss-of-function mutations in CDK10 or CycM cause Al Kaissi and STAR syndromes, respectively.
- Two specific mutations may allow truncated CDK10 and CycM variants to be expressed.
Purpose of the Study:
- To functionally characterize two truncated CDK10/CycM variants.
- To assess their heterodimerization, kinase activity, and stability.
- To understand their role in Al Kaissi and STAR syndromes.
Main Methods:
- Structural modeling to predict heterodimer formation.
- In vitro kinase assays.
- Yeast two-hybrid interaction studies.
- Expression and stability analysis in human cells.
Main Results:
- Both truncated variants successfully formed CDK10/CycM heterodimers.
- The CycM variant partially activated CDK10 in vitro; the CDK10 variant remained inactive.
- Truncated variants showed significant proteasomal degradation in human cells.
Conclusions:
- Al Kaissi syndrome is linked to a complete loss of CDK10/CycM activity.
- STAR syndrome is associated with a partial loss of CDK10/CycM activity.
- Proteasomal degradation contributes to the loss of function in these syndromes.
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