Controlling the Caspases

  title={Controlling the Caspases},
  author={Stephen W. Fesik and Yigong Shi},
  pages={1477 - 1478}
Enzymes called caspases are the executioners of programmed cell death. The IAP (inhibitor of apoptosis) proteins suppress apoptosis by blocking caspase activity and this suppression can be relieved by Smac/DIABLO, a mitochondrial protein released into the cytosol in response to apoptotic stimuli. In their Perspective, Fesik and Shi discuss recent structural and biochemical studies that reveal the molecular basis for the inhibition of caspases by IAPs and the relief of IAP inhibition by Smac… 
Molecular mechanisms of caspase regulation during apoptosis
The present understanding of caspase regulation during apoptosis is described and biochemical and structural studies have led to important advances in understanding the underlying molecular mechanisms of cispase regulation.
The Mechanism of Apoptosis Regulation by IAP Antagonist Smac/DIABLO
The role of caspases and IAPs in apoptosis is reviewed and the mechanism of apoptosis regulation by IAP antagonist Smac is focused on.
Caspases and apoptosis.
This work has shown that a subset of caspases has evolved to participate in the activation of pro-inflammatory cytokines, and thus members of the caspase family participate in one of two very distinct intracellular signalling pathways.
Apoptosis: IAP proteins: blocking the road to death's door
The functional and structural properties of the IAP gene family, a group of structurally related proteins that, in addition to their ability to suppress apoptotic cell death, are involved in an increasing number of seemingly unrelated cellular functions, are reviewed.
Mechanism of XIAP-mediated inhibition of caspase-9.
Essential Roles of the Bcl-2 Family of Proteins in Caspase-2-induced Apoptosis*
It is shown that proteolytic activation of Bid and the subsequent induction of the mitochondrial apoptotic pathway through Bax/Bak is essential for apoptosis triggered by caspase-2.
Reaper Is Regulated by IAP-mediated Ubiquitination*
It is shown that the Drosophila RHG proteins (Reaper, HID, and Grim) are themselves substrates for IAP-mediated ubiquitination of Reaper, demonstrating a novel function for I APs and suggesting that IAPs and Reaper-like proteins mutually control each other's abundance.
Structural studies of proteins in apoptosis and lipid signaling
Signaling pathways control the fate of the cell. For example, they promote cell survival or commit the cell to death (apoptosis) in response to cell injury or developmental stimuli, decisions, whic


Structural and biochemical basis of apoptotic activation by Smac/DIABLO
It is shown that Smac/DIABLO promotes not only the proteolytic activation of procaspase-3 but also the enzymatic activity of mature caspases, both of which depend upon its ability to interact physically with IAPs.
IAP family proteins--suppressors of apoptosis.
Although the mechanism used by the IAPs to suppress cell death remains debated, several studies have provided insights into the biochemical functions of these intriguing proteins and a variety of reports have suggested an important role for the I APs in some human diseases.
Molecular Determinants of the Caspase-promoting Activity of Smac/DIABLO and Its Role in the Death Receptor Pathway*
Evidence that Smac/DIABLO functions at the levels of both the Apaf-1-caspase-9 apoptosome and effector caspases and expression of a cytosolic SmAC/DiaBLO in Type II cells allowed TRAIL to bypass Bcl-xL inhibition of death receptor-induced apoptosis is provided.
A Single BIR Domain of XIAP Sufficient for Inhibiting Caspases*
Findings identify BIR2 as the minimal caspase-inhibitory domain of XIAP and indicate that a single BIR domain can be sufficient for binding and inhibiting caspases.
Biochemical pathways of caspase activation during apoptosis.
This review focuses on the two most well-studied pathways of caspase activation: the cell surface death receptor pathway and the mitochondria-initiated pathway.
The inhibitor of apoptosis, cIAP2, functions as a ubiquitin-protein ligase and promotes in vitro monoubiquitination of caspases 3 and 7.
The inhibitor of apoptosis, cIAP2, contains a putative Ring finger motif at the C terminus that possesses intrinsic ubiquitin ligase activity and promotes substrate-independent ubiquitination.