|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 52, 50834-50841, December 27, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Apoptosis Section, Regulation of Cell Growth Laboratory,
NCI, National Institutes of Health, Frederick, Maryland 21702
Complex networks of signaling pathways control
the apoptotic response and, therefore, cell survival. However, these
networks converge on a common machinery, of which the caspase
cysteine proteases are key components. Diverse apoptotic stimuli
release holocytochrome c from mitochondria, allowing
holocytochrome c to bind apoptotic protease activating
factor-1 (Apaf-1), which in turn binds caspase-9 both activating this
caspase and forming an Apaf-1/caspase-9 holoenzyme. Cytochrome
c lacking heme (the apo form) cannot support caspase
activation, although the reason for this has not been studied. Here we
show that apocytochrome c still binds Apaf-1 and that it
can block holo-dependent caspase activation in a cell-free
system. In addition we show that overexpression of apocytochrome
c blocks Bax-induced apoptosis in cells. Thus it is
possible to modulate cell survival by interfering with the Apaf-1/cytochrome c interaction. Given the key role played
by Apaf-1/cytochrome c in the apoptotic process, and the
role of apoptosis in degenerative disease, this interaction may
serve as a novel therapeutic target.
Apocytochrome c Blocks Caspase-9 Activation and
Bax-induced Apoptosis*
*
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.
To whom correspondence should be addressed. Tel.: 301-846-6140;
Fax: 301-846-1666; E-mail: hfearnhead@ncifcrf.gov.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  T. V. A. Murray, J. M. McMahon, B. A. Howley, A. Stanley, T. Ritter, A. Mohr, R. Zwacka, and H. O. Fearnhead A non-apoptotic role for caspase-9 in muscle differentiation J. Cell Sci., November 15, 2008; 121(22): 3786 - 3793. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yano, S. Nakamuta, X. Wu, Y. Okumura, and H. Kido A Novel Function of 14-3-3 Protein: 14-3-3{zeta} Is a Heat-Shock-related Molecular Chaperone That Dissolves Thermal-aggregated Proteins Mol. Biol. Cell, November 1, 2006; 17(11): 4769 - 4779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Guerra, L. A. Lopez-Fernandez, M. A. Garcia, A. Zaballos, and M. Esteban Human Gene Profiling in Response to the Active Protein Kinase, Interferon-induced Serine/threonine Protein Kinase (PKR), in Infected Cells: INVOLVEMENT OF THE TRANSCRIPTION FACTOR ATF-3 IN PKR-INDUCED APOPTOSIS J. Biol. Chem., July 7, 2006; 281(27): 18734 - 18745. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Najera, C. E. Gomez, E. Domingo-Gil, M. M. Gherardi, and M. Esteban Cellular and Biochemical Differences between Two Attenuated Poxvirus Vaccine Candidates (MVA and NYVAC) and Role of the C7L Gene. J. Virol., June 1, 2006; 80(12): 6033 - 6047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kawai, A. Lal, X. Yang, S. Galban, K. Mazan-Mamczarz, and M. Gorospe Translational Control of Cytochrome c by RNA-Binding Proteins TIA-1 and HuR Mol. Cell. Biol., April 15, 2006; 26(8): 3295 - 3307. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |