CDK6 is activated by the atypical cyclin I to promote E2F-mediated gene expression and cancer cell proliferation

Eva Quandt1, Núria Masip1, Sara Hernández-Ortega1

  • 1Basic Science Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain.

Molecular Oncology
|April 21, 2023
PubMed

Insights

Researchers discovered a new cyclin, cyclin I (CCNI), that partners with CDK6 to drive cancer cell proliferation. This finding reveals a novel mechanism in cell cycle regulation and offers potential therapeutic targets for breast cancer.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Cyclin-dependent kinases (CDKs) and cyclins are key cell cycle regulators.
  • Atypical cyclins possess unique structures, but their CDK partners are often unknown.

Purpose of the Study:

  • To identify novel atypical cyclin-CDK complexes using a yeast two-hybrid screen.
  • To investigate the role of the CDK6-CCNI complex in cancer cell proliferation.

Main Methods:

  • Yeast two-hybrid screening to identify protein interactions.
  • In vitro and in vivo assays to assess cell proliferation.
  • Gene silencing and drug treatment (palbociclib) to validate findings.
  • Analysis of gene expression in cancer cell lines and patient samples.

Main Results:

  • Identified 10 new cyclin-CDK complexes, including CDK6-CCNI.
  • The CDK6-CCNI complex phosphorylates the retinoblastoma protein.
  • CCNI upregulation enhances breast cancer cell proliferation, similar to cyclin D.
  • CCNI downregulation reduces cell number and S-phase entry.
  • CCNI upregulation correlates with E2F target gene expression in breast cancer.

Conclusions:

  • Cyclin I (CCNI) is identified as a novel partner for CDK6.
  • The CDK6-CCNI complex promotes cell cycle progression and cancer cell proliferation.
  • CCNI represents a new target for modulating CDK6 activity in cancer therapy.

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