Related Experiment Video

Updated: Mar 26, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

9.5K

Caspases uncouple p27(Kip1) from cell cycle regulated degradation and abolish its ability to stimulate cell migration

S R Podmirseg1, H Jäkel1, G D Ranches1

  • 1Division of Medical Biochemistry; Biocenter; Innsbruck Medical University; Innsbruck, Austria.

Oncogene
|February 2, 2016
PubMed

Insights

Caspases stabilize the cell cycle inhibitor p27(Kip1) by cleaving it, preventing degradation. This caspase-mediated stabilization promotes cell cycle exit and influences cytoskeletal remodeling during differentiation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Caspases are known for programmed cell death but also have non-lethal roles in development.
  • The CDK inhibitor p27(Kip1) is crucial for terminal cell cycle exit and differentiation.
  • p27(Kip1) levels are regulated by SCF-Skp2-mediated degradation.

Purpose of the Study:

  • To investigate the non-lethal functions of caspases in regulating p27(Kip1) during cell differentiation.
  • To identify how caspase activity impacts p27(Kip1) stability and its role in cell cycle control and cytoskeletal dynamics.

Main Methods:

  • Identification of a novel caspase cleavage site in human p27(Kip1).
  • Analysis of p27(Kip1) processing by caspases and its effect on SCF-Skp2-mediated degradation.
  • Assessment of p27(Kip1)'s interaction with RhoA and its impact on cell motility and invasion.

Main Results:

  • A novel caspase cleavage site was identified in p27(Kip1), removing a 22-amino acid C-terminal fragment.
  • Caspase processing protects p27(Kip1) from SCF-Skp2 degradation, stabilizing it during cell cycle phases S, G2, and M.
  • Processed p27(Kip1) loses its ability to bind RhoA, inhibiting RhoA activation and thus cell migration and invasion.

Conclusions:

  • Caspase-mediated stabilization of p27(Kip1) contributes to cell cycle exit during differentiation.
  • The altered interaction with RhoA following caspase processing impacts cytoskeletal remodeling, further supporting non-lethal roles of caspases in development.

More Related Videos

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila13:21

In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila

Published on: November 27, 2016

9.6K
Evaluation of Caspase Activation to Assess Innate Immune Cell Death10:23

Evaluation of Caspase Activation to Assess Innate Immune Cell Death

Published on: January 20, 2023

3.9K

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
14.5K
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...
6.2K
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

5.6K
Cancer Cell Migration through Invadopodia01:35

Cancer Cell Migration through Invadopodia

Invadosome is a broad category of cell surface structures with proteolytic activity that  degrades the extracellular matrix (ECM). Invadosomes are present in normal cell types, including macrophages, endothelial cells, and neurons, as well as tumor cells. Although the macrophage podosomes and tumor cell invadopodia are classified as invadosomes, they have different structures, molecular pathways, and functions. Podosomes are short structures that last for a few minutes. However,...
3.5K
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.
38.9K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
9.2K