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Cytochrome c and dATP-Dependent Formation of Apaf-1/Caspase-9 Complex Initiates an Apoptotic Protease Cascade
TLDR
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. Expand
Autoactivation of procaspase-9 by Apaf-1-mediated oligomerization.
TLDR
It is shown that deletion of the Apaf-1 WD-40 repeats makes Apf-1 constitutively active and capable of processing procaspase-9 independent of cytochrome c/dATP and oligomerizing its precursor molecules. Expand
Identification of Omi/HtrA2 as a Mitochondrial Apoptotic Serine Protease That Disrupts Inhibitor of Apoptosis Protein-Caspase Interaction*
TLDR
The results provide clear evidence for the involvement of a mitochondrial serine protease in the apoptotic pathway, emphasizing the critical role of the mitochondria in cell death. Expand
Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells.
TLDR
The discovery of HA14-1, a small molecule and nonpeptidic ligand of a Bcl-2 surface pocket, provides a chemical probe to study B cl-2-regulated apoptotic pathways in vivo and could lead to the development of new therapeutic agents. Expand
Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected].
TLDR
A mechanism for NEMO's critical role in IKK activation is provided, and a key to understanding the link between cytokine-receptor proximal signalling and IKK and NF-kappaB activation is understood. Expand
Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi
TLDR
Structural and biochemical observations provide an important framework for deciphering the mechanisms of HtrA2/Omi-mediated apoptosis and reveal a pyramid-shaped homotrimer mediated exclusively by the serine protease domains. Expand
A conserved XIAP-interaction motif in caspase-9 and Smac/DIABLO regulates caspase activity and apoptosis
TLDR
It is shown that XIAP associates with the active caspase-9–Apaf-1 holoenzyme complex through binding to the amino terminus of the linker peptide on the small subunit of caspite-9, which becomes exposed after proteolytic processing of procaspases-9 at Asp 315. Expand
IAPs block apoptotic events induced by caspase‐8 and cytochrome c by direct inhibition of distinct caspases
TLDR
It is demonstrated that IAPs can suppress different apoptotic pathways by inhibiting distinct caspases and identify pro‐caspase‐9 as a new target for IAP‐mediated inhibition of apoptosis. Expand
Caspase-2 Induces Apoptosis by Releasing Proapoptotic Proteins from Mitochondria*
TLDR
It is shown 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 and it is found that Bcl-2 and BCl-xL can block caspases-2- and CRADD-induced cell death. Expand
Negative regulation of the Apaf-1 apoptosome by Hsp70
TLDR
It is proposed that resistance to apoptosis exhibited by stressed cells and some tumours, which constitutively express high levels of Hsp70, may be due in part to modulation of Apaf-1 function by HSp70. Expand
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