Caspases are a crucial element in the process of apoptosis. They are a type of enzyme called proteases and have a cysteine molecule in the active site. Their target proteins are specific aspartic acids. Caspases are made within the cell as an inactive form, procaspases. Activation occurs by proteolytic cleavage at one or two aspartic acids and catalysed by activated caspases. Each activated caspase molecule will cleave many procaspase molecules. Once activated an amplifying proteolytic cascade is formed thus activating other procaspases.
The leakage of Cytochrome C from the mitochondrial intermembrane space initiates the activation of the first caspases. In apoptosis, there are two forms of caspase that are used: initiator caspases (caspase-8,-9) and executioner caspases (-3,-6 and -7). Initiator pro-caspases will be activated first, and then go onto cleave and activate the executioner pro-caspases.
The activated caspases progress apoptosis by cleaving nuclear lamins, which leads to nuclear fragmentation. DNase is activated and fragments the cell DNA and DNase inhibitor is cleaved. The cell detaches from its neighbours through caspases cleaving the cytoskeleton. This leads to loss of communication with the extracellular matrix."
Several caspases are mediators of innate immune response (caspase-1, -4, -5, -12 in humans and caspase-1, -11, and -12 in mice).
Caspases belong to a subfamily of proteases known as endopeptidases which cleave target proteins at specific aspartic acids. They hydrolyze peptide bonds C-terminally in aspartate residues. The caspases have cysteine at their active site and are named due to the 'C' for cysteine and the 'asp' for aspartic acid. Caspases are synthesised in the cell as procaspases.
Caspases and Apoptosis
Capases are responsible for the programmed death of a cell. In their inactive state caspases are present as zymogens, precaspases or blocked by specific caspases inhibitors. When apoptosis is triggered the caspases activate each other forming a cascade. The signal becomes amplified along the cascade and leads to the death of the cell.
- ↑ David R. McIlwain, Thorsten Berger and Tak W. Mak http://cshperspectives.cshlp.org/content/5/4/a008656.full
- ↑ http://www.ncbi.nlm.nih.gov/pubmed/12101390
- ↑ Marks F, Klingmuller U, Muller-Decker K, (2009) Cellular Signalling Processing 1st edition page Garland Science 2009
- ↑ Alberts et al (2008) Molecular Biology of the Cell, 6th Edition, New York: Garland Science