Related Experiment Video

Updated: May 30, 2026

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
06:00

Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics

Published on: May 14, 2016

Cdk2 acts upstream of mitochondrial permeability transition during paclitaxel-induced apoptosis

Xiao-Xi Guo1, Hanna Kim, Yang Li

  • 1Key Laboratory for Molecular Enzymology & Engineering of the Ministry of Education, Jilin University, Changchun 130012, China.

Protein & Cell
|August 9, 2011
PubMed

Insights

Cyclin-dependent kinase 2 (Cdk2) activity regulates early apoptosis stages. Inhibiting Cdk2 prevents mitochondrial damage and cell death, suggesting Cdk2

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cyclin-dependent kinases (Cdks) sequentially regulate the mammalian cell cycle.
  • Apoptosis, or programmed cell death, is a critical cellular process.
  • Paclitaxel is a chemotherapy drug that induces apoptosis.

Purpose of the Study:

  • To investigate the role of cyclin-dependent kinase 2 (Cdk2) in paclitaxel-induced apoptosis.
  • To determine if Cdk2 regulates early events in apoptosis, such as mitochondrial membrane potential (MMP) loss and cytochrome c release.

Main Methods:

  • Utilized paclitaxel to induce apoptosis in cells.
  • Employed ectopic expression of dominant-negative Cdk2 (Cdk2-dn) and Cdk2 inhibitor p21(WAF1/CIP1).
  • Overexpressed cyclin A to force Cdk2 activation.
  • Assessed MMP, cytochrome c release, and caspase-3 activation.

Main Results:

  • Upregulation of Cdk2 activity correlated with loss of MMP during paclitaxel-induced apoptosis.
  • Cdk2 inhibition suppressed MMP loss, cytochrome c release, and caspase-3 activation.
  • Forced Cdk2 activation by cyclin A overexpression promoted these apoptotic events.
  • Cdk2 activation did not affect downstream events initiated by Bax-induced cytochrome c release.

Conclusions:

  • Cdk2 kinase regulates apoptosis at stages preceding mitochondrial permeability transition and cytochrome c release.
  • Cdk2 plays a critical role in the early signaling pathways of paclitaxel-induced apoptosis.
  • Targeting Cdk2 may offer a therapeutic strategy to modulate apoptosis in cancer treatment.

More Related Videos

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel08:29

Long-term Live-cell Imaging to Assess Cell Fate in Response to Paclitaxel

Published on: May 14, 2018

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk113:15

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1

Published on: February 25, 2016

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...
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...
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...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...