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Stains

Caspases


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 6 February 2012, last major update February 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

Definition
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● Cysteine proteases that act as essential initiators and executioners of apoptosis; also involved in necrosis and inflammation (Wikipedia)
● Also called Cysteine-ASPartic proteASES or Cysteine-dependent ASPartate-directed proteASES
● Act as apoptotic cell death effectors by cleaving polypeptides on the carboxyl end of aspartate residues
● Synthesized as inactive proenzymes, may be activated by other caspases (initiator caspases), which cause a cascade of activation similar to coagulation or complement
● Caspases are signaling proteases, designed for specific protein cleavage and not for protein degradation; they make one or two cuts in their target proteins and do not destroy protein structure, but rather modify it, thus creating gain or loss of function events that drive forward the apoptotic phenotype (J Cell Sci 2010;123:3209)
● Final targets are nuclear lamins, ICAD/DFF45 (inhibitor of caspase activated DNase or DNA fragmentation factor 45), PARP (poly-ADP ribose polymerase), PAK2 (P 21-activated kinase 2)
● Cleavage of ICAD allows the release of CAD, which relocalizes from the cytoplasm to the nucleus, where it cleaves genomic DNA

Diagrams
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Intrinisic and extrinsic pathways


Various images


Caspase 3


General
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● Final common pathway effector caspase that carries out apoptosis; its presence means that apoptosis has not only been initiated but also occurred
● Interacts with upstream caspases 8 and 9 (Wikipedia)
● Cleaves PARP and ICAD
● Cleaved caspase 3 (CCP-3) is the large fragment (17/19 kDa) of activated caspase 3 resulting from cleavage adjacent to Asp175; may have prognostic value if present in >10% of tumor cells in some malignancies

Uses for pathologists
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● Immunohistochemical marker of apoptosis (J Histochem Cytochem 2002;50:449)

Micro images
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Detection of cleaved caspase 3


Cleaved caspase 3 in granular cell tumors


Caspase 7

General
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● Involved in execution stage of apoptosis
● Has similarities with caspase 3 (Int J Biochem Cell Biol 2010;42:21)

Diagrams
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Structure of pro-caspase 7 and caspase 7



Caspase 8

General
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● Initiator caspase, also cleaves Bid, a bcl2 homolog that activates caspase 9 by releasing cytochrome C from mitochondria
● Has important role in CD95-mediated activation of MAPKs (Cell Death Dis 2011;2:e212)

Uses by pathologists
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● Marker of initiation of apopotosis


Caspase 9

General
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● Initiates activation of caspase 3, 6 and 7

Diagrams
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Regulation of the Apaf-1-caspase-9 apoptosome

End of Stains > Caspases


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