Related Experiment Video

Updated: May 25, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

p27(Kip1) controls cytokinesis via the regulation of citron kinase activation

Murielle P Serres1, Uta Kossatz, Yong Chi

  • 1INSERM UMR1037, Cancer Research Center of Toulouse, Toulouse, France.

The Journal of Clinical Investigation
|February 2, 2012
PubMed

Insights

The tumor suppressor p27 normally inhibits cell division. However, a modified p27 (p27(CK-)) promotes tumors by disrupting cell division through interaction with citron kinase, revealing a novel role in cytokinesis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • p27(Kip1) (p27) is a known tumor suppressor that inhibits cyclin-cyclin-dependent kinase (cyclin-CDK) activity.
  • Mice with a mutated p27 unable to inhibit cyclin-CDK (p27(CK-)) exhibit increased tumor incidence, suggesting an oncogenic role for p27.

Purpose of the Study:

  • To investigate the non-canonical functions of p27 beyond cyclin-CDK inhibition.
  • To elucidate the role of p27 in cell cycle regulation, specifically in cytokinesis and its potential link to tumor development.

Main Methods:

  • Analysis of p27(CK-) mice for phenotypes like multinucleation and polyploidy.
  • Assessment of cytokinesis and abscission defects in mouse embryonic fibroblasts expressing p27(CK-).
  • Identification and characterization of p27-interacting proteins, including citron kinase (citron-K), using in vitro and in vivo assays.

Main Results:

  • p27(CK-) mice displayed multinucleation and polyploidy, phenotypes absent in p27(-/-) mice, indicating a G2/M role independent of cyclin-CDK inhibition.
  • p27(CK-) expression induced cytokinesis and abscission defects in mouse embryonic fibroblasts.
  • p27 directly interacts with citron-K at the contractile ring and mid-body during cell division. p27 binding to citron-K inhibits RhoA activation, crucial for cytokinesis.

Conclusions:

  • p27 plays a critical role in regulating cytokinesis through its interaction with citron-K, independent of its canonical cyclin-CDK inhibitory function.
  • Dysregulation of the p27-citron-K interaction contributes to multinucleation, polyploidy, and potentially tumor development.
  • This study uncovers a novel mechanism by which p27 influences cell division and tumor suppression via the RhoA/citron-K pathway.

More Related Videos

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis08:33

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

Quantitative Immunofluorescence Assay to Measure the Variation in Protein Levels at Centrosomes09:39

Quantitative Immunofluorescence Assay to Measure the Variation in Protein Levels at Centrosomes

Published on: December 20, 2014

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
Separation of Sister Chromatids02:17

Separation of Sister Chromatids

At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
At the onset of anaphase, separase, a proteolytic enzyme, is...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...