Regulation of the Intrinsic Apoptosis Pathway by Reactive Oxygen Species
Chu Chiao Wu,Shawn B. Bratton +1 more
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TLDR
A large, multimeric complex is composed of the adapter protein, apoptotic protease-activating factor-1, and the cysteine protease, caspase-9, which stimulates formation of the "apoptosome" in stressed cells.Abstract:
Significance: The intrinsic apoptosis pathway is conserved from worms to humans and plays a critical role in the normal development and homeostatic control of adult tissues. As a result, numerous diseases from cancer to neurodegeneration are associated with either too little or too much apoptosis. Recent Advances: B cell lymphoma-2 (BCL-2) family members regulate cell death, primarily via their effects on mitochondria. In stressed cells, proapoptotic BCL-2 family members promote mitochondrial outer membrane permeabilization (MOMP) and cytochrome c (cyt c) release into the cytoplasm, where it stimulates formation of the “apoptosome.” This large, multimeric complex is composed of the adapter protein, apoptotic protease-activating factor-1, and the cysteine protease, caspase-9. Recent studies suggest that proteins involved in the processes leading up to (and including) formation of the apoptosome are subject to various forms of post-translational modification, including proteolysis, phosphorylation,...read more
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References
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Journal ArticleDOI
The BCL-2 protein family: opposing activities that mediate cell death
TL;DR: New insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, but a unifying hypothesis for the mechanisms they use to activate caspases remains elusive.
Journal ArticleDOI
Tumor suppressor p53 is a direct transcriptional activator of the human bax gene
T Miyashita,John C. Reed +1 more
TL;DR: The bax gene promoter region contains four motifs with homology to consensus p53-binding sites and wild-type but not mutant p53 protein bound to oligonucleotides corresponding to this region of the bax promoter, suggesting that bax is a p53 primary-response gene, presumably involved in a p 53-regulated pathway for induction of apoptosis.
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Regulation of Cell Death Protease Caspase-9 by Phosphorylation
Michael H. Cardone,Natalie Roy,Henning R. Stennicke,Guy S. Salvesen,Thomas F. Franke,Eric J. Stanbridge,Steven M. Frisch,John C. Reed +7 more
TL;DR: In this paper, the kinase Akt and p21-Ras, an Akt activator, induced phosphorylation of pro-caspase-9 (pro-Casp9) in cells.
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Apaf-1, a Human Protein Homologous to C. elegans CED-4, Participates in Cytochrome c–Dependent Activation of Caspase-3
TL;DR: The purification and cDNA cloning of Apaf-1, a novel 130 kd protein from HeLa cell cytosol that participates in the cytochrome c-dependent activation of caspase-3, leading to apoptosis is reported here.
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Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1.
Masao Saitoh,Hideki Nishitoh,Makiko Fujii,Kohsuke Takeda,Kei Tobiume,Yasuhiro Sawada,Masahiro Kawabata,Kohei Miyazono,Hidenori Ichijo +8 more
TL;DR: Evidence that Trx is a negative regulator of ASK1 suggests possible mechanisms for redox regulation of the apoptosis signal transduction pathway as well as the effects of antioxidants against cytokine‐ and stress‐induced apoptosis.