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CDK11 requires a critical activator SAP30BP to regulate pre-mRNA splicing

Changshou Wang1, Lin Xu1, Chen Du2

  • 1Key Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

The EMBO Journal
|December 7, 2023
PubMed

Insights

SAP30BP is identified as a crucial activator for CDK11 (cyclin-dependent kinase 11), a key target in cancer therapy. This interaction is vital for regulating pre-mRNA splicing, impacting cell cycle progression in cancer cells.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • CDK11 (cyclin-dependent kinase 11) is a promising target for cancer therapy due to its roles in cell cycle progression and phosphorylation of transcription/splicing factors.
  • CDK11 activation requires cyclin L1 or L2, but other regulatory mechanisms remain largely unknown.

Purpose of the Study:

  • To investigate novel regulators of CDK11 activity.
  • To elucidate the role of SAP30BP in CDK11 function and its impact on pre-mRNA splicing.

Main Methods:

  • Co-immunoprecipitation to study protein complex formation.
  • In vitro kinase assays to assess CDK11 activity.
  • In vivo degradation studies to evaluate protein stability and function.
  • Analysis of pre-mRNA splicing defects.

Main Results:

  • SAP30BP forms a stable complex with CDK11 and cyclins L1/L2.
  • SAP30BP degradation leads to defects in pre-mRNA splicing, similar to CDK11 loss.
  • SAP30BP enhances CDK11 kinase activity by stabilizing cyclin L1/L2 association with CDK11.
  • SAP30BP is essential for maintaining global pre-mRNA splicing.

Conclusions:

  • SAP30BP is identified as a critical activator of CDK11.
  • SAP30BP plays a vital role in regulating global pre-mRNA splicing through CDK11 modulation.
  • These findings highlight SAP30BP as a potential therapeutic target in conjunction with CDK11 for cancer treatment.
Keywords:
CDK11SAP30BPcyclin Lpre-mRNA splicing

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