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Updated: Jun 9, 2026

Analysis of Cell Cycle Position in Mammalian Cells
Published on: January 21, 2012
Cyclin D1 blocks the anti-proliferative function of RUNX3 by interfering with RUNX3-p300 interaction
Kazunori Iwatani1, Tetsuhiro Fujimoto, Takaaki Ito
1Division of Pathology and Experimental Medicine, Graduate School of Life Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto-shi 861-8556, Japan.
Abstract:
Transcriptional function of cyclin D1, whose deregulation is frequently observed in human cancers, has been suggested to contribute to cancer formation. In the present study, we show that cyclin D1 protein inhibits RUNX3 activity by directly binding to it and interfering with its interaction with p300 interaction in lung cancer cells. Cyclin D1 inhibits p300-dependent RUNX3 acetylation and negatively regulates cyclin-dependent kinase (cdk) inhibitor p21 expression. These transcriptional effects of cyclin D1 do not require cdk4/6 kinase activation. We propose that cyclin D1 provides a transcriptional switch that allows the tumor suppressor activity of RUNX3 to be repressed in cancer cells. Since RUNX3 plays tumor suppressive roles in a wide range of cancers, a non-canonical cyclin D1 function may be critical for neoplastic transformation of the epithelial cells in which RUNX3 regulates proliferation.
Insights
Cyclin D1 protein suppresses RUNX3
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- Deregulation of cyclin D1 is common in human cancers.
- Cyclin D1's transcriptional functions are implicated in cancer development.
- RUNX3 acts as a tumor suppressor in various cancers.
Purpose of the Study:
- To investigate the non-canonical transcriptional role of cyclin D1 in lung cancer.
- To elucidate the mechanism by which cyclin D1 affects RUNX3 activity.
- To determine if cyclin D1's function is kinase-dependent.
Main Methods:
- Investigated protein-protein interactions between cyclin D1 and RUNX3.
- Assessed the impact of cyclin D1 on RUNX3 acetylation.
- Monitored the expression of cyclin-dependent kinase (cdk) inhibitor p21.
- Examined the role of cdk4/6 kinase activity.
Main Results:
- Cyclin D1 directly binds to RUNX3, inhibiting its activity.
- Cyclin D1 interferes with RUNX3's interaction with p300.
- p300-dependent RUNX3 acetylation is inhibited by cyclin D1.
- Cyclin D1 negatively regulates p21 expression independently of cdk4/6 kinase activity.
Conclusions:
- Cyclin D1 acts as a transcriptional switch, repressing RUNX3 tumor suppressor activity in cancer cells.
- This non-canonical function of cyclin D1 may be crucial for epithelial cell neoplastic transformation.
- Understanding this mechanism offers potential therapeutic targets for cancers where RUNX3 is important.
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