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Updated: Aug 2, 2025

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
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.
Abstract:
Cyclin-dependent kinases (CDKs), together with their cyclin partners, are the master cell cycle regulators. Remarkably, the cyclin family was extended to include atypical cyclins, characterized by distinctive structural features, but their partner CDKs remain elusive. Here, we conducted a yeast two-hybrid screen to identify new atypical cyclin-CDK complexes. We identified 10 new complexes, including a complex between CDK6 and cyclin I (CCNI), which was found to be active against retinoblastoma protein. CCNI upregulation increased the proliferation of breast cancer cells in vitro and in vivo, with a magnitude similar to that seen upon cyclin D upregulation, an effect that was abrogated by CDK6 silencing or palbociclib treatment. In line with these findings, CCNI downregulation led to a decrease in cell number and a reduction in the percentage of cells reaching S phase. Finally, CCNI upregulation correlated with the high expression of E2F target genes in large panels of cancer cell lines and tissue samples from breast cancer patients. In conclusion, we unveil CCNI as a new player in the pathways that activate CDK6, enriching the wiring of cell cycle control.
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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