Related Experiment Video
Updated: Aug 19, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Functional activation of Nedd2/ICH-1 (caspase-2) is an early process in apoptosis
N L Harvey1, A J Butt, S Kumar
1Hanson Centre for Cancer Research, Institute of Medical and Veterinary Science, Rundle Mall, Adelaide, SA 5000, Australia.
Abstract:
The ICE/CED-3 family of proteases (caspases) play a central role in the execution phase of apoptosis. These proteases are synthesised as precursor molecules that require processing at specific aspartate residues to produce the two subunits that comprise the active enzyme. The activation of some of these proteases has been shown to occur during apoptosis. Here we show that Nedd2/ICH-1 (caspase-2) is activated during apoptosis induced by a variety of apoptotic stimuli. This activation occurs very early upon treatment of cells with apoptotic agents and appears to precede the activation of CPP32 (caspase-3). The activation of Nedd2 was not seen in cells that are resistant to apoptosis. These observations suggest that Nedd2 is an early effector in the pathway leading to cell death. Our observations also lend weight to the hypothesis that a group of caspases containing long prodomains are the first to be activated in response to apoptotic signals and that they lie upstream of a second class of caspases such as CPP32 containing short or no prodomains.
Insights
Nedd2 (caspase-2) is activated early during apoptosis, preceding caspase-3 activation. This suggests Nedd2 is an early effector in programmed cell death pathways.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Caspases are key proteases in apoptosis execution.
- Caspases are synthesized as inactive precursors requiring cleavage for activation.
- Some caspases activate during apoptosis.
Purpose of the Study:
- To investigate the activation of Nedd2/ICH-1 (caspase-2) during apoptosis.
- To determine the timing of Nedd2 activation relative to other caspases.
Main Methods:
- Induction of apoptosis using various stimuli.
- Monitoring caspase activation.
- Comparing Nedd2 activation with CPP32 (caspase-3) activation.
Main Results:
- Nedd2 (caspase-2) activation was observed during apoptosis induced by diverse stimuli.
- Nedd2 activation occurred early, preceding CPP32 (caspase-3) activation.
- Nedd2 activation was absent in apoptosis-resistant cells.
Conclusions:
- Nedd2 (caspase-2) functions as an early effector in the apoptosis pathway.
- Long prodomain caspases, like Nedd2, may activate upstream of short prodomain caspases, such as CPP32.
Related Concept Videos
Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Apoptosis
Caspases
The Extrinsic Apoptotic Pathway
The Intrinsic Apoptotic Pathway
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...

