BCL-2, BCL-XL Sequester BH3 Domain-Only Molecules Preventing BAX- and BAK-Mediated Mitochondrial Apoptosis
Emily H. Cheng,Michael C. Wei,Solly Weiler,Richard A. Flavell,Tak W. Mak,Tullia Lindsten,Stanley J. Korsmeyer +6 more
TL;DR: In mammals, BH3 domain-only molecules activate multidomain proapoptotic members to trigger a mitochondrial pathway, which both releases cytochrome c to activate caspases and initiates caspase-independent mitochondrial dysfunction.
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About: This article is published in Molecular Cell. The article was published on 01 Sep 2001. and is currently open access. The article focuses on the topics: Mitochondrial apoptosis-induced channel & Bcl-2-associated X protein.
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Citations
Mechanisms of cytochrome c release by proapoptotic BCL-2 family members.
TL;DR: Data support a model in which the apoptotic pathway bifurcates following activation of a "BH3 only" family member, and proposed mechanisms by which proapoptotic BCL-2 family members induce cytochrome c release are reviewed.
754
BAX activation is initiated at a novel interaction site
Evripidis Gavathiotis,Motoshi Suzuki,Marguerite L. Davis,Marguerite L. Davis,Kenneth L. Pitter,Kenneth L. Pitter,Gregory H. Bird,Gregory H. Bird,Samuel G. Katz,Samuel G. Katz,Ho-Chou Tu,Hyungjin Kim,Emily H. Cheng,Nico Tjandra,Loren D. Walensky,Loren D. Walensky +15 more
TL;DR: It is demonstrated by NMR analysis that BIM SAHB binds BAX at an interaction site that is distinct from the canonical binding groove characterized for anti-apoptotic proteins, establishing a new target for therapeutic modulation of apoptosis.
Bcl-2-regulated apoptosis: mechanism and therapeutic potential.
Jerry M. Adams,Suzanne Cory +1 more
TL;DR: The Bcl-2 family may also regulate autophagy and mitochondrial fission/fusion, and its pro-survival members are attractive therapeutic targets in cancer and perhaps autoimmunity and viral infections.
711
The role of BH3-only proteins in the immune system.
TL;DR: This review describes BH3-only proteins, a pro-apoptotic subgroup of the BCL-2 family, and their role in the development and function of the immune system.
687
The role of mitochondrial factors in apoptosis: a Russian roulette with more than one bullet.
TL;DR: This review summarises and evaluates the current knowledge concerning the complex role of released mitochondrial proteins in the apoptotic process and identifies members of the Bcl-2 protein family that control the integrity and response of mitochondria to apoptotic signals.
References
Mitochondria and apoptosis
Douglas R. Green,John C. Reed +1 more
TL;DR: A variety of key events in apoptosis focus on mitochondria, including the release of caspase activators (such as cytochrome c), changes in electron transport, loss of mitochondrial transmembrane potential, altered cellular oxidation-reduction, and participation of pro- and antiapoptotic Bcl-2 family proteins.
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Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade
Peng Li,Deepak Nijhawan,Imawati Budihardjo,Srinivasa M. Srinivasula,Manzoor Ahmad,Emad S. Alnemri,Xiaodong Wang +6 more
TL;DR: Mutation of the active site of caspase-9 attenuated the activation of cazase-3 and cellular apoptotic response in vivo, indicating that casp enzyme-9 is the most upstream member of the apoptotic protease cascade that is triggered by cytochrome c and dATP.
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Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death
TL;DR: Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line and counters the death repressor activity of B cl-2, suggesting a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.
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Bid, a Bcl2 Interacting Protein, Mediates Cytochrome c Release from Mitochondria in Response to Activation of Cell Surface Death Receptors
TL;DR: The purification of a cytosolic protein that induces cytochrome c release from mitochondria in response to caspase-8, the apical caspases activated by cell surface death receptors such as Fas and TNF is reported.
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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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