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In response to many different apoptotic stimuli, cytochrome c is released from the intermembrane space of the mitochondria into the cytoplasm, where it serves as a cofactor in the activation of procaspase 9. Inhibition of this process can occur either by preventing cytochrome c release or by blocking caspase activation or activity. Experiments involving in vitro reconstitution of apoptosis in cell-free extracts of Xenopus laevis eggs have suggested that extracts arrested in interphase are susceptible to an endogenous apoptotic program leading to caspase activation, whereas extracts arrested in meiotic metaphase are not. We report here that Mos/MEK/MAPK pathways active in M phase-arrested eggs are responsible for rendering them refractory to apoptosis. Interestingly, M phase-arrested extracts are competent to release cytochrome c, yet still do not activate caspases. Concomitantly, we have also demonstrated that recombinant Mos, MEK, and ERK are sufficient to block cytochrome c-dependent caspase activation in purified Xenopus cytosol, which lacks both transcription and translation. These data indicate that the MAP kinase pathway can target and inhibit post-cytochrome c release apoptotic events in the absence of new mRNA/protein synthesis and that this biochemical pathway is responsible for the apoptotic inhibition observed in meiotic X. laevis egg extracts.
Bergmann,
The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling.
1998, Pubmed
Bergmann,
The Drosophila gene hid is a direct molecular target of Ras-dependent survival signaling.
1998,
Pubmed Bonni,
Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms.
1999,
Pubmed Cain,
Apaf-1 oligomerizes into biologically active approximately 700-kDa and inactive approximately 1.4-MDa apoptosome complexes.
2000,
Pubmed Chau,
Aven, a novel inhibitor of caspase activation, binds Bcl-xL and Apaf-1.
2000,
Pubmed Chu,
A novel enhancer of the Apaf1 apoptosome involved in cytochrome c-dependent caspase activation and apoptosis.
2001,
Pubmed Desagher,
Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis.
1999,
Pubmed Deshmukh,
Evidence of a novel event during neuronal death: development of competence-to-die in response to cytoplasmic cytochrome c.
1998,
Pubmed Deveraux,
IAP family proteins--suppressors of apoptosis.
1999,
Pubmed Deveraux,
IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases.
1998,
Pubmed Du,
Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition.
2000,
Pubmed Earnshaw,
Apoptosis. A cellular poison cupboard.
1999,
Pubmed Erhardt,
B-Raf inhibits programmed cell death downstream of cytochrome c release from mitochondria by activating the MEK/Erk pathway.
1999,
Pubmed Evans,
Reaper-induced apoptosis in a vertebrate system.
1997,
Pubmed
,
Xenbase Faure,
A member of the Ste20/PAK family of protein kinases is involved in both arrest of Xenopus oocytes at G2/prophase of the first meiotic cell cycle and in prevention of apoptosis.
1997,
Pubmed
,
Xenbase Goyal,
Induction of apoptosis by Drosophila reaper, hid and grim through inhibition of IAP function.
2000,
Pubmed Green,
Mitochondria and apoptosis.
1998,
Pubmed Griffiths,
Cell damage-induced conformational changes of the pro-apoptotic protein Bak in vivo precede the onset of apoptosis.
1999,
Pubmed Gross,
Caspase cleaved BID targets mitochondria and is required for cytochrome c release, while BCL-XL prevents this release but not tumor necrosis factor-R1/Fas death.
1999,
Pubmed Gross,
BCL-2 family members and the mitochondria in apoptosis.
1999,
Pubmed Guadagno,
Requirement for MAPK activation for normal mitotic progression in Xenopus egg extracts.
1998,
Pubmed
,
Xenbase Haccard,
Induction of metaphase arrest in cleaving Xenopus embryos by MAP kinase.
1993,
Pubmed
,
Xenbase Hensey,
A developmental timer that regulates apoptosis at the onset of gastrulation.
1997,
Pubmed
,
Xenbase Hetman,
Neuroprotection by brain-derived neurotrophic factor is mediated by extracellular signal-regulated kinase and phosphatidylinositol 3-kinase.
1999,
Pubmed Holmström,
MAPK/ERK signaling in activated T cells inhibits CD95/Fas-mediated apoptosis downstream of DISC assembly.
2000,
Pubmed Hu,
Role of cytochrome c and dATP/ATP hydrolysis in Apaf-1-mediated caspase-9 activation and apoptosis.
1999,
Pubmed Jiang,
Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf-1.
2000,
Pubmed Kluck,
The pro-apoptotic proteins, Bid and Bax, cause a limited permeabilization of the mitochondrial outer membrane that is enhanced by cytosol.
1999,
Pubmed
,
Xenbase Kluck,
Cytochrome c activation of CPP32-like proteolysis plays a critical role in a Xenopus cell-free apoptosis system.
1997,
Pubmed
,
Xenbase Li,
Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade.
1997,
Pubmed Li,
Cleavage of BID by caspase 8 mediates the mitochondrial damage in the Fas pathway of apoptosis.
1998,
Pubmed Luo,
Bid, a Bcl2 interacting protein, mediates cytochrome c release from mitochondria in response to activation of cell surface death receptors.
1998,
Pubmed Newmeyer,
Cell-free apoptosis in Xenopus egg extracts: inhibition by Bcl-2 and requirement for an organelle fraction enriched in mitochondria.
1994,
Pubmed
,
Xenbase Palmer,
The activation of MAP kinase and p34cdc2/cyclin B during the meiotic maturation of Xenopus oocytes.
2000,
Pubmed
,
Xenbase Porter,
Emerging roles of caspase-3 in apoptosis.
1999,
Pubmed Roy,
The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases.
1997,
Pubmed Sagata,
The c-mos proto-oncogene product is a cytostatic factor responsible for meiotic arrest in vertebrate eggs.
1989,
Pubmed
,
Xenbase Srinivasula,
Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization.
1998,
Pubmed Stack,
Developmentally regulated activation of apoptosis early in Xenopus gastrulation results in cyclin A degradation during interphase of the cell cycle.
1997,
Pubmed
,
Xenbase Vaux,
Cell death in development.
1999,
Pubmed Verhagen,
Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins.
2000,
Pubmed Vucic,
Inhibitor of apoptosis proteins physically interact with and block apoptosis induced by Drosophila proteins HID and GRIM.
1998,
Pubmed Vucic,
Inhibition of reaper-induced apoptosis by interaction with inhibitor of apoptosis proteins (IAPs).
1997,
Pubmed Watanabe,
Independent inactivation of MPF and cytostatic factor (Mos) upon fertilization of Xenopus eggs.
1991,
Pubmed
,
Xenbase Yew,
Meiotic initiation by the mos protein in Xenopus.
1992,
Pubmed
,
Xenbase Zou,
An APAF-1.cytochrome c multimeric complex is a functional apoptosome that activates procaspase-9.
1999,
Pubmed
