What is a Caspase?

Jillian O Keeffe

A caspase, or cysteine aspartate-specific protease, is one of a group of enzymes involved in cell death. Each types has a particular role in cell death, or apoptosis, as it is technically known. Caspases are proteins that cut, or cleave, other proteins at a specific point.

Caspases are a family of inactive proenzymes that play a crucial role in cell apoptosis, which is the scheduled death of cells.
Caspases are a family of inactive proenzymes that play a crucial role in cell apoptosis, which is the scheduled death of cells.

There are 14 human caspases. Each enzyme can be placed into one of three groups, depending on the job it does. Caspase 2, 8, 9 and 10 are activator enzymes. They begin the process of apoptosis by cleaving and activating other caspases.

The group known as the executioner group has three members, Caspase 3, 6 and 7. Executioner versions cut cellular proteins to break down the cell. Members of the third group are known as cytokine processors. This group contains the seven remaining caspases, and they signal the immune system to start the process of inflammation to clean up the bits of dead cell.

These enzymes are known as cysteine aspartate-specific proteases because each one cuts another protein at a specific site. All proteins are made up of a sequence of amino acids, and caspases cut proteins after an aspartate amino acid. Each type recognizes the proteins it is supposed to cut by reading the three amino acids present in the sequence before the aspartate.

Caspases are present in each cell in inactive forms known as zymogens. When other molecules, called death receptors, in the cell signal to the activator caspases that apoptosis is to begin, the zymogen activator caspases are cleaved and activated. The activators begin what is called the caspase cascade, during which different caspases activate each other when necessary. The cascade can also be activated by molecules released from the mitochondria of the cell or by the enzyme Granzyme B, which is released from cell-killing T-cells.

The caspases cleave the structural proteins of the cell to break it down. For example, Caspase 6 breaks down laminins, the structural proteins of the nucleus. They do not just destroy proteins; sometimes they affect other cellular enzymes.

Caspase 3 cleaves a complex that is normally inactive in the cell, releasing a deoxyribonuclease (DNAse) enzyme. This Caspase-Activated DNAse (CAD) breaks DNA into pieces. It also prevents an enzyme involved in DNA repair, poly ADP-ribose polymerase (PARP), from repairing the DNA damage. To do this, the caspase cleaves the PARP enzyme, rendering it inactive.

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