Omi/HtrA2 Promotes Cell Death by Binding and Degrading the Anti-apoptotic Protein ped/pea-15
Copyright policy )Omi/HtrA2 Promotes Cell Death by Binding and Degrading the Anti-apoptotic Protein ped/pea-15
ped/pea-15 is a ubiquitously expressed 15-kDa protein featuring a broad anti-apoptotic function. In a yeast two-hybrid screen, the pro-apoptotic Omi/HtrA2 mitochondrial serine protease was identified as a specific interactor of the ped/pea-15 death effector domain. Omi/HtrA2 also bound recombinant ped/pea-15 in vitro and co-precipitated with ped/pea-15 in 293 and HeLa cell extracts. In these cells, the binding of Omi/HtrA2 to ped/pea-15 was induced by UVC exposure and followed the mitochondrial release of Omi/HtrA2 into the cytoplasm. Upon UVC exposure, cellular ped/pea-15 protein expression levels decreased. This effect was prevented by the ucf-101 specific inhibitor of the Omi/HtrA2 proteolytic activity, in a dose-dependent fashion. In vitro incubation of ped/pea-15 with Omi/HtrA2 resulted in ped/pea-15 degradation. In intact cells, the inhibitory action of ped/pea-15 on UVC-induced apoptosis progressively declined at increasing Omi/HtrA2 expression. This further effect of Omi/HtrA2 was also inhibited by ucf-101. In addition, ped/pea-15 expression blocked Omi/HtrA2 co-precipitation with the caspase inhibitor protein XIAP and caspase 3 activation. Thus, in part, apoptosis following Omi/HtrA2 mitochondrial release is mediated by reduction in ped/pea-15 cellular levels. The ability of Omi/HtrA2 to relieve XIAP inhibition on caspases is modulated by the relative levels of Omi/HtrA2 and ped/pea-15.
- University Federico II of Naples Italy
- National Research Council Italy
- Institute Experimental Endocrinology and Oncology Italy
- University of Sannio Italy
- University of Central Florida United States
STRUCTURAL BASIS, SMAC/DIABLO, Biochemistry & Molecular Biology, Cytoplasm, DNA, Complementary, Blotting, Western, Apoptosis, Enzyme-Linked Immunosorbent Assay, GLUCOSE-TRANSPORT, Cell Line, Mitochondrial Proteins, XIAP, MITOCHONDRIA, KINASE, Humans, CASPASE ACTIVITY, Gene Library, Glutathione Transferase, Dose-Response Relationship, Drug, Caspase 3, Intracellular Signaling Peptides and Proteins, INHIBITOR, High-Temperature Requirement A Serine Peptidase 2, Phosphoproteins, Mitochondria, Enzyme Activation, SERINE-PROTEASE, Caspases, OUTER-MEMBRANE, Apoptosis Regulatory Proteins, HeLa Cells
STRUCTURAL BASIS, SMAC/DIABLO, Biochemistry & Molecular Biology, Cytoplasm, DNA, Complementary, Blotting, Western, Apoptosis, Enzyme-Linked Immunosorbent Assay, GLUCOSE-TRANSPORT, Cell Line, Mitochondrial Proteins, XIAP, MITOCHONDRIA, KINASE, Humans, CASPASE ACTIVITY, Gene Library, Glutathione Transferase, Dose-Response Relationship, Drug, Caspase 3, Intracellular Signaling Peptides and Proteins, INHIBITOR, High-Temperature Requirement A Serine Peptidase 2, Phosphoproteins, Mitochondria, Enzyme Activation, SERINE-PROTEASE, Caspases, OUTER-MEMBRANE, Apoptosis Regulatory Proteins, HeLa Cells
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).85 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!