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Updated: Sep 26, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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Abolishment of the interaction between cyclin-dependent kinase 2 and Cdk-associated protein phosphatase by a

Chau-Ting Yeh1, Su-Chuan Lu, Chung-Hao Chao

  • 1Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, 199, Tung Hwa North Road, Taipei 105, Taiwan. catyeh@ms14.hinet.net

Biochemical and Biophysical Research Communications
|May 15, 2003
PubMed

Insights

Researchers discovered a new interaction domain between cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) and Cdk2. Truncated KAP mutants containing this domain disrupt the normal KAP-Cdk2 interaction, offering insights into phosphatase regulation.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Cell Biology

Background:

  • Cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual-specificity phosphatase.
  • KAP dephosphorylates Cdk2 at threonine 160 in a cyclin-dependent manner.
  • Aberrant KAP transcripts are found in hepatocellular carcinoma.

Purpose of the Study:

  • To investigate aberrant KAP transcripts in hepatoblastoma cells.
  • To identify the KAP-Cdk2 interaction domain.
  • To determine the functional impact of truncated KAP mutants.

Main Methods:

  • Yeast two-hybrid and co-immunoprecipitation assays to identify interaction domains.
  • Yeast three-hybrid system to assess functional interference.
  • Analysis of KAP transcripts in HepG2 hepatoblastoma cell line.

Main Results:

  • Aberrant KAP transcripts with distinct deletions were identified in HepG2 cells.
  • A novel KAP-Cdk2 interaction domain was mapped to amino acids 1-34 of KAP.
  • Truncated KAP mutants encoding this domain inhibited wild-type KAP-Cdk2 interaction.

Conclusions:

  • A previously unknown KAP-Cdk2 interaction domain was discovered.
  • Truncated KAP mutants can interfere with the wild-type KAP-Cdk2 interaction.
  • These findings provide new insights into KAP-Cdk2 regulation and potential roles in hepatoblastoma.

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