TY  - JOUR
AU  - Slee, EA
AU  - Harte, MT
AU  - Kluck, RM
AU  - Wolf, BB
AU  - Casiano, CA
AU  - Newmeyer, DD
AU  - Wang, HG
AU  - Reed, JC
AU  - Nicholson, DW
AU  - Alnemri, ES
AU  - Green, DR
AU  - Martin, SJ
Y2  - 2020/12/21
Y1  - 1999/01/25
SN  - 0021-9525
UR  - http://hdl.handle.net/11343/257116
AB  - Exit of cytochrome c from mitochondria into the cytosol has been implicated as an important step in apoptosis. In the cytosol, cytochrome c binds to the CED-4 homologue, Apaf-1, thereby triggering Apaf-1-mediated activation of caspase-9. Caspase-9 is thought to propagate the death signal by triggering other caspase activation events, the details of which remain obscure. Here, we report that six additional caspases (caspases-2, -3, -6, -7, -8, and -10) are processed in cell-free extracts in response to cytochrome c, and that three others (caspases-1, -4, and -5) failed to be activated under the same conditions. In vitro association assays confirmed that caspase-9 selectively bound to Apaf-1, whereas caspases-1, -2, -3, -6, -7, -8, and -10 did not. Depletion of caspase-9 from cell extracts abrogated cytochrome c-inducible activation of caspases-2, -3, -6, -7, -8, and -10, suggesting that caspase-9 is required for all of these downstream caspase activation events. Immunodepletion of caspases-3, -6, and -7 from cell extracts enabled us to order the sequence of caspase activation events downstream of caspase-9 and reveal the presence of a branched caspase cascade. Caspase-3 is required for the activation of four other caspases (-2, -6, -8, and -10) in this pathway and also participates in a feedback amplification loop involving caspase-9.
LA  - English
PB  - ROCKEFELLER UNIV PRESS
T1  - Ordering the cytochrome c-initiated caspase cascade: Hierarchical activation of caspases-2, -3, -6, -7, -8, and -10 in a caspase-9-dependent manner
DO  - 10.1083/jcb.144.2.281
IS  - The Journal of Cell Biology
VL  - 144
IS  - 2
SP  - 281-292
L1  - /bitstream/handle/11343/257116/PMC2132895.pdf?sequence=1&isAllowed=y
ER  -