Related Experiment Video

Updated: Aug 9, 2026

Analysis of Cell Cycle Position in Mammalian Cells
12:19

Analysis of Cell Cycle Position in Mammalian Cells

Published on: January 21, 2012

Skp2-dependent degradation of p27kip1 is essential for cell cycle progression

Uta Kossatz1, Nils Dietrich, Lars Zender

  • 1Department of Gastroenterology, Hepatology and Endocrinology and Institute for Molecular Biology, Hannover Medical School, Hannover, Germany.

Genes & Development
|November 3, 2004
PubMed

Insights

Loss of skp2 E3 ligase causes cell defects, but restoring its substrate p27kip1 normalizes hepatocyte function. This highlights p27kip1

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • SCF(skp2) E3 ligase activity is crucial for degrading cell cycle and transcriptional regulators.
  • Loss of skp2 in mice results in abnormal cell size, DNA content, and proliferation.

Purpose of the Study:

  • To investigate the role of skp2 substrate p27kip1 in the skp2 knockout mouse phenotype.
  • To define the critical period of p27kip1 action in G1 phase cell cycle progression.

Main Methods:

  • Comparison of skp2 knockout and p27T187A knock-in mouse models.
  • Analysis of p27kip1 turnover kinetics and cell cycle progression.

Main Results:

  • Loss of p27kip1 reverts the skp2 knockout hepatocyte phenotype to normal.
  • A specific G1 window exists where p27kip1 blocks cell cycle exit from quiescence.
  • Impaired p27kip1 turnover during G1 prevents cell division, causing compensatory growth.

Conclusions:

  • p27kip1 is a key mediator of the skp2 knockout phenotype.
  • Regulating p27kip1 turnover in early G1 is critical for normal cell division.

More Related Videos

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

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

Related Concept Videos

Negative Regulator Molecules01:23

Negative Regulator Molecules

Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
DNA Damage can Stall the Cell Cycle02:36

DNA Damage can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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...
DNA Damage Can Stall the Cell Cycle02:36

DNA Damage Can Stall the Cell Cycle

In response to DNA damage, cells can pause the cell cycle to assess and repair the breaks. However, the cell must check the DNA at certain critical stages during the cell cycle. If the cell cycle pauses before DNA replication, the cells will contain twice the amount of DNA. On the other hand, if cells arrest after DNA replication but before mitosis, they will contain four times the normal amount of DNA. With a host of specialized proteins at their disposal,cells must use the right protein at...
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...
The Cell Cycle Control System01:28

The Cell Cycle Control System

The cell cycle regulation directs how a cell proceeds from one phase to the next and begins mitosis. The cell cycle control system includes intracellular regulatory molecules and external triggers. They provide "stop" or "advance" signals and operate at specific cell cycle stages termed checkpoints to ensure that a particular process is completed before the cell advances to the next phase.
Cyclins and cyclin-dependent kinases (Cdks) are the primary cell cycle regulators and function at the cell...