The key difference between caspase 3 and cleaved caspase 3 is that caspase 3 is the inactive precursor that is also known as procaspase 3, while cleaved caspase 3 is the activated form of caspase 3 needed for cell apoptosis.
Caspases (Cystein-aspartic acid proteases) are a group of protease enzymes needed in the process of programmed cell death (apoptosis). This process is essential in maintaining the balance of cell survival and cell death of multicellular organisms. However, cells secrete all the caspases in the inactivated form to avoid unnecessary cellular deaths. There are two types of caspases: initiator caspases (caspases 8 and 9) and executioner caspases (caspases 3, 6, and 7). Initiator caspases detect the apoptotic signals, and executioner caspases are involved in the actual disintegration of the cell. Therefore, initiator caspases are activated by external stimuli like DNA damage and cellular stress, while executioner caspases, including caspase 3, are activated mainly by the initiator caspases.
CONTENTS
1. Overview and Key Difference
2. What is Caspase 3
3. What is Cleaved Caspase 3
4. Similarities – Caspase 3 and Cleaved Caspase 3
5. Caspase 3 vs. Cleaved Caspase 3 in Tabular Form
6. FAQ – Caspase 3 and Cleaved Caspase 3
7. Summary – Caspase 3 vs. Cleaved Caspase 3
What is Caspase 3?
Caspase 3 is an important executioner caspase and is present in the cytosol as dimers. Each monomer has a molecular weight of 32 kDa and comprises 277 amino acid residues. The CASP3 gene on the chromosomal location 4q35 encodes this protein.

Figure 01: Caspase 3
Caspase 3 is initially synthesized in its inactive/zymogenic state and is therefore referred to as procaspase 3. It is organized into two subunits (p20 and p10) connected by a linker region and an N-terminal pro-domain similar to other caspases. In this state, caspase 3 lacks protease activity until the pro-domain is removed during activation.
What is Cleaved Caspase 3?
Cleaved caspase-3 refers to the active form of caspase-3, which is generated through the cleavage of the pro-domain during apoptosis. This process initiates once the initiator caspases (8/9) interact with inactive caspase 3 and cleave at the D175 amino acid at the linker region. Cleavage results in conformational changes to expose the active sites of caspase 3, allowing substrate recognition. Finally, the N terminal pro-domain is removed to form an activated cleaved caspase 3. This activated caspase 3 then targets nuclear proteins and cytoplasmic proteins, leading to programmed cell death.
What are the Similarities Between Caspase 3 and Cleaved Caspase 3?
- Caspase 3 and cleaved caspase 3 are acid proteases.
- They are crucial mediators of programmed cell death.
- They share a common origin.
- Both are proteins and comprise the same amino acid sequences except the N-terminal pro-domain.
- Both are cysteine-aspartic acid protease enzymes that play a pivotal role in cellular apoptosis.
- They serve as markers for studying apoptosis.
What is the Difference Between Caspase 3 and Cleaved Caspase 3?
Caspase 3 is in the zymogen state, while cleaved caspase 3 is in the active state. Thus, this is the key difference between caspase 3 and cleaved caspase 3. Structurally, caspase 3 consists of an N-terminal pro-domain, and its substrate recognition active sites are hidden. On the other hand, cleaved caspase 3 lacks an N-terminal pro-domain, and its active site is exposed. Moreover, caspase 3 is found as dimers in the cytosol, while cleaved caspase 3 may be found in various cellular sites depending on the site of action.
The infographic below presents the differences between caspase 3 and cleaved caspase 3 in tabular form for side-by-side comparison.
FAQ: Caspase 3 and Cleaved Caspase 3
What is meant by caspase?
Caspase refers to Cystein-aspartic acid protease enzymes.
How is caspase 3 activated?
Caspase-3 is activated through interaction with initiator caspases, involving conformational changes in the linker region and the removal of the inhibitory pro-domain.
What is the role of caspase 3 in apoptosis?
Caspase 3 acts as an executioner caspase in the caspase cascade once activated, leading to cell apoptosis.
Summary – Caspase 3 vs. Cleaved Caspase 3
Caspase 3 and cleaved caspase 3 are integral enzymes of programmed cell death. Caspase 3 is initially secreted in its inactive form, known as procaspase 3, which activates through initiator caspases. Both share similarities in amino acid sequences, origin, and role in apoptosis. However, differences can be identified in their activation states, protein structure, enzymatic activity, and regulatory mechanisms. So, this summarizes the difference between caspase 3 and cleaved caspase 3.
Reference:
1. “Caspase 3 – An Overview.” ScienceDirect Topics.
2. “Procaspase 3 – An Overview.” ScienceDirect Topics.
Image Courtesy:
1. “1rhj” By Deposition authors: Becker, J.W., Rotonda, J., Soisson, S.M.; visualization author: User: Astrojan – RCSB (CC BY-SA 4.0) via Commons Wikimedia
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