A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death.
X chromosome-linked inhibitor of apoptosis (XIAP) is an endogenous inhibitor of caspase-3, -7, and -9. Smac/DIABLO, an inhibitor of XIAP, is released from mitochondria upon receiving apoptotic stimuli and binds to the BIR2 and BIR3 domains of XIAP, thereby inhibiting its caspase-inhibitory activity. Here we report that a serine protease called HtrA2/Omi is released from mitochondria and inhibits the function of XIAP by direct binding in a similar way to Smac. Moreover, when overexpressed extramitochondrially, HtrA2 induces atypical cell death, which is neither accompanied by a significant increase in caspase activity nor inhibited by caspase inhibitors, including XIAP. A catalytically inactive mutant of HtrA2, however, does not induce cell death. In short, HtrA2 is a Smac-like inhibitor of IAP activity with a serine protease-dependent cell death-inducing activity.
Pubmed ID: 11583623 RIS Download
Amino Acid Sequence | Apoptosis | Carrier Proteins | Caspase Inhibitors | Caspases | Cell Fractionation | Cell Line | Cloning, Molecular | Genes, Reporter | Humans | Intracellular Signaling Peptides and Proteins | Microscopy, Fluorescence | Mitochondria | Mitochondrial Proteins | Protein Binding | Protein Transport | Proteins | Recombinant Fusion Proteins | Serine Endopeptidases | Ultraviolet Rays | X-Linked Inhibitor of Apoptosis Protein