1. Caspases: Intracellular Signaling by Proteolysis
Guy S Salvesen, Vishva M Dixit 
Cell 
Volume 91, Issue 4, Pages (November 1997)
DOI: /S (00)

2. Figure 1 Schematic of a Processed Caspase
The active form of a caspase consists of large and small chains released from a precursor by proteolysis. A linker segment flanked by Asp resideus, and an N-terminal polypeptide (sometimes known as the prodomain) is also released from several caspases during activation, as in the example of caspase-1 shown above. The N-peptide is not conserved between caspases, but the two chains (shown in black) that fold to form the catalytic site contain extensive identities throughout the family.
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3. Figure 2 Human Caspase Family Relationships
Alignment of the catalytic domains demonstrates evolutionary relationships between the caspases that are mirrored to a variable extent by their substrate specificity groupings (Thornberry et al. 1997). The scale is in Myr, with an arbitrary cutoff at 50.
Cell  , DOI: ( /S (00) )

4. Figure 3 Life and Death Decisions
Death may be signaled by direct ligation of receptors at the cell surface, which leads to the activation of initiator caspases (8 or 10). These caspases then, directly or indirectly, activate the “executioner caspases” (3, 6, and 7). Alternatively, irreparable damage to the genome caused by mutagens, pharmaceuticals that inhibit DNA repair, or ionizing radiation—transmitted by a currently unknown mechanism—engages the same executioner caspases. The latter events progress through a pathway that is regulated by members of the Bcl2/Bax family, and which may result in the release of pro-apoptotic factors from mitochondria, for example (see for example,Kroemer et al. 1997; Liu et al. 1997). Input is integrated by a hypothetical entity—the “apostat” (Bredesen 1996)—that makes decisions for the fate of the cell. The search for chemical identity of the apostat represents somewhat of a “holy grail” in cell death research.
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5. Figure 4 Intervention Points on the Apoptotic Pathway
Though usually studied following Fas ligation, the pathway is also engaged through activation of caspase zymogens by granzyme B and, hypothetically, other ectopic proteases. Once activated, the caspases are sensitive to inhibition by the viral products CrmA and p35, and perhaps more significantly from the point of normal reglation, by endogenous inhibitors such as XIAP. The pro- and anti-apoptotic proteins of the Bcl2/Bax family do not directly affect caspase activity, and are thought to intervene upstream of the executioner caspases.
Cell  , DOI: ( /S (00) )