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J. Biol. Chem., Vol. 277, Issue 16, 13430-13437, April 19, 2002
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From the Center for Apoptosis Research and the Department of
Microbiology and Immunology, Kimmel Cancer Institute, Thomas Jefferson
University, Philadelphia, Pennsylvania 19107
Caspase-2 is one of the earliest identified
caspases, but the mechanism of caspase-2-induced apoptosis remains
unknown. We show here that caspase-2 engages the
mitochondria-dependent apoptotic pathway by inducing the
release of cytochrome c (Cyt c) and other mitochondrial apoptogenic factors into the cell cytoplasm. In support
of these observations we found that Bcl-2 and Bcl-xL can block
caspase-2- and CRADD (caspase and RIP adaptor with death domain)-induced cell death. Unlike caspase-8, which can process all known caspase zymogens directly, caspase-2 is completely inactive toward other caspase zymogens. However, like caspase-8, physiological levels of purified caspase-2 can cleave cytosolic Bid protein, which in
turn can trigger the release of Cyt c from isolated
mitochondria. Interestingly, caspase-2 can also induce
directly the release of Cyt c, AIF
(apoptosis-inducing factor), and Smac (second mitochondria-derived activator of caspases protein) from isolated mitochondria independent of Bid or other cytosolic factors. The caspase-2-released Cyt c is sufficient to activate the Apaf-caspase-9 apoptosome
in vitro. In combination, our data suggest that caspase-2
is a direct effector of the mitochondrial apoptotic pathway.
Caspase-2 Induces Apoptosis by Releasing Proapoptotic Proteins
from Mitochondria*
,
*
This work was supported in part by National Institutes of
Health Grant AG14357 (to E. S. A.).The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
A Special Fellow of the Leukemia and Lymphoma Society.
§
Present address: INSERM U408, Faculté de Médecine
Xavier Bichat, Paris, France.
¶
To whom correspondence should be addressed: Thomas Jefferson
University, Kimmel Cancer Institute, Bluemle Life Sciences Bldg., Rm.
904, 233 S. 10th St., Philadelphia, PA 19107. Tel.: 215-503-4632; Fax:
215-923-1098; E-mail: E_Alnemri@lac.jci.tju.edu.
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|
|
|
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|
|
|
|
|
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|
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|
|
|
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|
|
|
|
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|
|
|
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|
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|
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|
|
|
|
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|
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|
|
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|
|
|
 |
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|
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|
|
|
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|
|
 |
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|
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|
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M. J. Pe |
