scholarly journals Diablo Promotes Apoptosis by Removing Miha/Xiap from Processed Caspase 9

2001 ◽  
Vol 152 (3) ◽  
pp. 483-490 ◽  
Author(s):  
Paul G. Ekert ◽  
John Silke ◽  
Christine J. Hawkins ◽  
Anne M. Verhagen ◽  
David L. Vaux
Keyword(s):  
Cell Death ◽  
Cytochrome C ◽  
Caspase 3 ◽  
Direct Interaction ◽  
Inhibitor Of Apoptosis ◽  
Caspase 9 ◽  
Inhibitor Of Apoptosis Protein ◽  
Grim Reaper ◽  
Apoptosis Protein ◽  
Mammalian Protein

MIHA is an inhibitor of apoptosis protein (IAP) that can inhibit cell death by direct interaction with caspases, the effector proteases of apoptosis. DIABLO is a mammalian protein that can bind to IAPs and antagonize their antiapoptotic effect, a function analogous to that of the proapoptotic Drosophila molecules, Grim, Reaper, and HID. Here, we show that after UV radiation, MIHA prevented apoptosis by inhibiting caspase 9 and caspase 3 activation. Unlike Bcl-2, MIHA functioned after release of cytochrome c and DIABLO from the mitochondria and was able to bind to both processed caspase 9 and processed caspase 3 to prevent feedback activation of their zymogen forms. Once released into the cytosol, DIABLO bound to MIHA and disrupted its association with processed caspase 9, thereby allowing caspase 9 to activate caspase 3, resulting in apoptosis.

Resistance of bone marrow-derived macrophages to apoptosis is associated with the expression of X-linked inhibitor of apoptosis protein in primary cultures of bone marrow cells

2001 ◽  
Vol 353 (2) ◽  
pp. 299-306 ◽  
Author(s):  
Hong LIN ◽  
Catheryne CHEN ◽  
Ben D.-M. CHEN
Keyword(s):  
Bone Marrow ◽  
Caspase 3 ◽  
Bone Marrow Cells ◽  
Primary Cultures ◽  
Precursor Cells ◽  
Inhibitor Of Apoptosis ◽  
Caspase 9 ◽  
Prolonged Incubation ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

In this study we investigated the underlying mechanisms that confer resistance on mature macrophages with the use of macrophage colony-stimulating factor (M-CSF)-induced bone marrow-derived macrophages (BMDM). In the presence of M-CSF, immature precursor cells were induced to undergo proliferation and differentiation into mature macrophages in vitro with cell morphology similar to that of tissue macrophages by day 7Ő10. Immunoblot analyses showed that bone marrow precursors express appreciable levels of caspase-3 and caspase-9 but no or very low levels of c-fms (M-CSF receptor) and the apoptosis regulators X-linked inhibitor of apoptosis protein (XIAP), c-IAP-1, Bcl-2 and Bax. The differentiation of BMDM is associated with a steady and gradual increase in the levels of c-fms, XIAP, c-IAP-1, Bcl-2 and Bax, reaching maximal levels by day 7. However, the levels of caspase-3 and caspase-9 stayed essentially unchanged even after prolonged incubation (more than 10 days) with M-CSF. Unlike bone marrow precursor cells, mature BMDM (day 7Ő10) were resistant to apoptosis induced by M-CSF depletion, which includes the activation of caspase-3 and caspase-9 and the degradation of XIAP, Bcl-2 and Bax proteins in the process. Treatment of day 7 BMDM with XIAP anti-sense oligonucleotides (oligos), but not sense oligos, partly abolished their resistance to apoptosis. By using a gel-shift assay and a specific nuclear factor κB (NF-κB) inhibitor, we demonstrated that NF-κB activity is responsible for the up-regulation of XIAP in M-CSF-treated macrophages. In addition, treatment of starved macrophages with M-CSF induced a rapid phosphorylation of Akt kinase before the activation of NF-κB. Our results showed that XIAP is one of the anti-apoptotic regulators that confer resistance on mature macrophages by M-CSF.

scholarly journals Pseudomonas aeruginosaDelays Kupffer Cell Death via Stabilization of the X-Chromosome-Linked Inhibitor of Apoptosis Protein

2007 ◽  
Vol 179 (1) ◽  
pp. 505-513 ◽  
Author(s):  
Alix Ashare ◽  
Martha M. Monick ◽  
Amanda B. Nymon ◽  
John M. Morrison ◽  
Matthew Noble ◽  
...  
Keyword(s):  
Cell Death ◽  
X Chromosome ◽  
Kupffer Cell ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein

scholarly journals X-linked inhibitor of apoptosis protein and active caspase-3 expression patterns in antral follicles in the sheep ovary

Reproduction ◽  
2011 ◽  
Vol 142 (6) ◽  
pp. 855-867 ◽  
Author(s):  
Hollian R Phillipps ◽  
Ilona C Kokay ◽  
David R Grattan ◽  
Peter R Hurst
Keyword(s):  
Mrna Expression ◽  
Caspase 3 ◽  
Expression Patterns ◽  
Inhibitor Of Apoptosis ◽  
Mrna Levels ◽  
Follicular Atresia ◽  
Inhibitor Of Apoptosis Protein ◽  
Antral Follicles ◽  
Apoptosis Protein ◽  
Active Caspase

X-linked inhibitor of apoptosis protein (XIAP) interacts with caspases to inhibit their activity, thereby providing a potential mechanism for regulation of granulosa cell apoptosis occurring during follicular atresia. The aim of this study was to determine the presence and localization of XIAP mRNA and protein content in the sheep ovary and compare these expression patterns with active caspase-3 protein in the same antral follicles. Romney ewe estrous cycles (n=25) were synchronized with 2–3 Estrumate injections and ovarian tissue collected during the luteal and follicular phases of the cycle. The presence ofXIAPmRNA was confirmed by RT-PCR using laser capture microdissected ovarian cell samples.XIAPmRNA was subsequently localized byin situhybridization histochemistry and XIAP and active caspase-3 protein visualized by immunohistochemistry. In antral follicles extensive XIAP localization was evident in both granulosa and thecal cells. In contrast, mRNA expression was widespread in granulosa cells and only detected in thecal tissue from a small proportion of antral follicles. Active caspase-3 and XIAP comparative expression analysis showed positiveXIAPmRNA expression in all late luteal phase (day 14) follicles, despite varying levels of active caspase-3 protein. A proportion of follicular phase (days 15 and 16) follicles, however, showed an inverse expression relationship at the protein and mRNA levels in both granulosa and thecal tissue, as did XIAP protein in day 14 follicles. These results suggest high XIAP may prevent activation of caspase-3, thereby regulating follicular atresia in antral follicles and could potentially be utilized as a marker of follicular health.

scholarly journals Molecular Cloning of ILP-2, a Novel Member of the Inhibitor of Apoptosis Protein Family

2001 ◽  
Vol 21 (13) ◽  
pp. 4292-4301 ◽  
Author(s):  
Bettina W. M. Richter ◽  
Samy S. Mir ◽  
Lisa J. Eiben ◽  
Jennifer Lewis ◽  
Stephanie Birkey Reffey ◽  
...  
Keyword(s):  
Molecular Cloning ◽  
Inhibitor Of Apoptosis ◽  
Physical Interaction ◽  
Caspase 9 ◽  
Inhibitor Of Apoptosis Protein ◽  
Normal Tissues ◽  
Apoptosis Protein ◽  
Processed Form

ABSTRACT Inhibitor of apoptosis protein (IAP)-like protein-1 (ILP-1) (also known as X-linked IAP [XIAP] and mammalian IAP homolog A [MIHA]) is a potent inhibitor of apoptosis and exerts its effects, at least in part, by the direct association with and inhibition of specific caspases. Here, we describe the molecular cloning and characterization of a human gene related to ILP-1, termed ILP-2. Despite high homology to ILP-1, ILP-2 is encoded by a distinct gene, which in normal tissues is expressed solely in testis. In contrast to ILP-1, overexpression of ILP-2 had no protective effect on apoptosis mediated by Fas (also known as CD95) or tumor necrosis factor. However, ILP-2 potently inhibited apoptosis induced by overexpression of Bax or by coexpression of caspase 9 with Apaf-1, and preincubation of cytosolic extracts with ILP-2 abrogated caspase activation in vitro. A processed form of caspase 9 could be coprecipitated with ILP-2 from cells, suggesting a physical interaction between ILP-2 and caspase 9. Thus, ILP-2 is a novel IAP family member with restricted specificity for caspase 9.

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