Related Experiment Video

Updated: Aug 11, 2026

Analysis of Cell Cycle Position in Mammalian Cells
12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

Cdk2 is dispensable for cell cycle inhibition and tumor suppression mediated by p27(Kip1) and p21(Cip1)

Alberto Martín1, Junko Odajima, Sarah L Hunt

  • 1Molecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.

Cancer Cell
|June 14, 2005
PubMed

Insights

Cyclin-dependent kinase 2 (Cdk2) is not essential for cell cycle inhibition by p27(Kip1) and p21(Cip1). These proteins suppress tumors and cell division independently of Cdk2 activity.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • p27(Kip1) and p21(Cip1) are known inhibitors of cell cycle progression.
  • They are believed to function by inhibiting Cdk2-cyclin E/A kinases.
  • Cdk2 is considered dispensable for mitotic cell division.

Purpose of the Study:

  • To investigate the role of Cdk2 in the inhibitory functions of p27(Kip1) and p21(Cip1).
  • To determine if Cdk2 is a necessary target for cell cycle inhibition and tumor suppression mediated by these proteins.

Main Methods:

  • Analysis of Cdk2-deficient (Cdk2-/-) fibroblasts.
  • Ectopic expression of p27(Kip1) or p21(Cip1) in Cdk2-/- cells.
  • Assessment of cell cycle progression and proliferation.
  • Evaluation of p21(Cip1)-induced cell cycle arrest after DNA damage.
  • Study of Cdk2 ablation in p27(Kip1) null mice.

Main Results:

  • p27(Kip1) and p21(Cip1) inhibited cell cycle progression in Cdk2-/- fibroblasts.
  • Loss of p27(Kip1) or p21(Cip1) provided similar proliferative advantages in both Cdk2(+/+) and Cdk2-/- cells.
  • Cdk2 was dispensable for p21(Cip1)-mediated cell cycle arrest post-DNA damage.
  • Ablation of Cdk2 did not rescue phenotypic defects in p27(Kip1) null mice, including pituitary tumors.

Conclusions:

  • Cdk2 is not an essential target for the cell cycle inhibitory effects of p27(Kip1) and p21(Cip1).
  • These proteins can suppress cell cycle progression and tumor growth independently of Cdk2.
  • The findings challenge the established model of Cdk2-dependent inhibition by p27(Kip1) and p21(Cip1).

More Related Videos

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols12:02

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Related Concept Videos

Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
Positive Regulator Molecules02:39

Positive Regulator Molecules

Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
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...
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...
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...
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...