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Executioner Caspases (Caspase 3, Caspase 6 and Caspase 7) Once initiator caspases are activated, they produce a chain reaction, activating several other executioner caspases. Executioner caspases degrade over 600 cellular components [19] in order to induce the morphological changes for apoptosis. Examples of caspase cascade during apoptosis:
Excessive apoptosis causes atrophy, whereas an insufficient amount results in uncontrolled cell proliferation, such as cancer. Some factors like Fas receptors and caspases promote apoptosis, while some members of the Bcl-2 family of proteins inhibit apoptosis. [7]
Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes that undergo proteolytic processing by upstream caspases (caspase-8, -9) at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme in the form of a ...
During apoptosis, the apoptotic effector caspase, caspase-3, cleaves ICAD and thus causes CAD to become activated. [7] A nucleosome, consisting of DNA (grey) wrapped around a histone tetramer (coloured). In apoptotic DNA fragmentation, the DNA is cleaved in the internucleosomal linker region, which is the part of the DNA not wrapped around the ...
[13] [16] In each case, caspase 9 activation leads to the activation of a full caspase cascade and subsequent cell death. It has been suggested that the evolutionary reason for the multimeric protein complex activating the caspase cascade is to ensure trace amounts of cytochrome c do not accidentally cause apoptosis. [7]
Caspase-3 has been found to be necessary for normal brain development as well as its typical role in apoptosis, where it is responsible for chromatin condensation and DNA fragmentation. [20] Elevated levels of a fragment of Caspase-3, p17, in the bloodstream is a sign of a recent myocardial infarction. [51]
Finally, perforin creates a pore in the membrane, and releases the caspases which leads to the activation of caspase 3. This initiator caspase may cause the cleaving of inactive caspase 3, causing it to become cleaved caspase 3. This is the final molecule needed to trigger cell death. [14]
Caspase-9 is an enzyme that in humans is encoded by the CASP9 gene.It is an initiator caspase, [5] critical to the apoptotic pathway found in many tissues. [6] Caspase-9 homologs have been identified in all mammals for which they are known to exist, such as Mus musculus and Pan troglodytes.