Disease relevance of BIRC2

• Apoptosis mediated by interleukin 1beta converting enzyme (ICE), which can be inhibited by Orgyia pseudotsugata nuclear polyhedrosis virus IAP (OpIAP) and cowpox virus crmA, was also inhibited by MIHA and MIHB [1].
• Akt activity in endometrial cancer cells: regulation of cell survival through cIAP-1 [2].
• A new family of human genes xiap, hiap-1 and hiap-2, which are homologous to the baculovirus iap (inhibitor of apoptosis) genes cp-iap and op-iap, has been recently cloned and shown to suppress apoptosis after serum withdrawal or exposure to a free radical inducer [3].
• Here, we report that human malignant glioma cell lines express XIAP, HIAP-1 and HIAP-2 mRNA and proteins [4].
• This was associated with more caspase-3 activity, a decline in the intracellular levels of XIAP, cIAP, and survivin, and apoptosis of ovarian cancer cells [5].

High impact information on BIRC2

• Serine protease inhibitors that block CIAP1 cleavage inhibit p53-dependent apoptosis [6].
• Human XIAP, cIAP1 and cIAP2 are direct inhibitors of at least two members of the caspase family of cell death proteases: caspase-3 and caspase-7 [7].
• The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases [8].
• Recombinant c-IAP-1 and c-IAP-2 also inhibited the activity of caspases-3 and -7 in vitro, with estimated Kis of <=0.1 microM, whereas NAIP did not [8].
• Similarly to XIAP, in vitro binding experiments indicated that c-IAP-1 and c-IAP-2 bound specifically to the terminal effector cell death proteases, caspases-3 and -7, but not to the proximal protease caspase-8, caspases-1 or -6 [8].

Biological context of BIRC2

• Similar results were obtained in intact cells when c-IAP-1 and c-IAP-2 were overexpressed by gene transfection, and apoptosis was induced by the anticancer drug, etoposide [8].
• Because TRAF2 regulates NF-kappaB activation, the effects of cIAP1 on TRAF2-mediated induction of NF-kappaB transcriptional activity were studied using reporter gene assays [9].
• Overexpression of Akt using a constitutively active Akt expression vector resulted in an up-regulation of cIAP-1 expression [2].
• Interestingly, apoptotic stimuli induced nuclear export of cIAP1, which was blocked by a chemical caspase inhibitor [10].
• cIAP1 Localizes to the nuclear compartment and modulates the cell cycle [10].

Anatomical context of BIRC2

• Utilizing a cell-free system in which caspases were activated in cytosolic extracts by addition of cytochrome c, c-IAP-1 and c-IAP-2 inhibited both the generation of caspase activities and proteolytic processing of pro-caspase-3 [8].
• CONCLUSION: The results demonstrate that CD40 engagement enhances eosinophil survival through induction of c-IAP2 expression and suggest a role for this mechanism in allergic inflammation [11].
• Sputum cells from asthmatic patients, unlike those from healthy subjects, substantially expressed CD40 and c-IAP2 [11].
• Chenodeoxycholic acid and taurochenodexycholic acid induce anti-apoptotic cIAP-1 expression in human hepatocytes [12].
• In dividing cells, cIAP1 was released into the cytosol early in mitosis, then reaccumulated in nuclei in late anaphase and in telophase, with the exception of a pool of cIAP1 that associated with the midbody [10].

Associations of BIRC2 with chemical compounds

• Apoptosis was assessed by staining with propidium iodide and FITC-conjugated annexin-V. c-IAP2 expression was inhibited with antisense oligonucleotides [11].
• Results: Chenodeoxycholic acid up-regulated both mRNA and protein expressions of cIAP-1 [12].
• The expression of apoptotic inhibitors (XIAP, cIAP-1, cIAP-2) and anti-apoptotic (Bcl-2) and pro-apoptotic (Bax) proteins was affected by vitamin E pretreatment [13].
• In particular, taurochenodeoxycholic acid (TCDCA), but not glycochenodeoxycholic acid (GCDCA), induced cIAP-1 mRNA expression [12].
• Moreover, CDCA-induced cIAP-1 mRNA expression was inhibited completely by calphostin C and SB203580, but not by wortmannin [12].

Physical interactions of BIRC2

• The cIAP BIR domains can be converted to tight binding caspase inhibitors by substituting these critical residues with XIAP residues [14].
• Co-immunoprecipitation assay showed that cIAP1 can interact with Fbxo7 in human cells [15].

Regulatory relationships of BIRC2

• IFN-gamma inhibition of TRAIL-induced IAP-2 upregulation, a possible mechanism of IFN-gamma-enhanced TRAIL-induced apoptosis [16].
• Furthermore, we showed that overexpression of Fbxo7 promotes the ubiquitination of cIAP1 [15].
• Furthermore, we showed that CD30-regulated expression of cIAP1 and cIAP2 was mediated by NFkappaB [17].
• The ubiquitin protein ligase activity of c-IAP1 is responsible for regulating the duration of TNF signaling in primary cells expressing TNFR2 [18].
• We demonstrate that TNFalpha-induced NF-kappaB activation is severely diminished in the absence of both c-IAP proteins [19].

Other interactions of BIRC2

• The presence of cIAP1 and Smac in LIGHT.LT beta R complex revealed a novel mechanism of LIGHT.LT beta R-induced apoptosis [20].
• Antisense knockdown of c-iap2 abolished CD40-induced enhancement of eosinophil survival [11].
• Conclusion: It was shown that CDCA induced cIAP-1 expression in hepatocytes through protein kinase C- and p38 mitogen-activated protein kinase-mediated pathway [12].
• Three members of the inhibitor of apoptosis protein (IAP) family, namely cellular (c)-IAP1, c-IAP2, and XIAP, and 2 antiapoptotic proteins of the Bcl-2 family, namely Bcl-x(L) and Bfl-1/A1, were investigated [11].
• Distinct BIR domains of cIAP1 mediate binding to and ubiquitination of tumor necrosis factor receptor-associated factor 2 and second mitochondrial activator of caspases [9].

Analytical, diagnostic and therapeutic context of BIRC2

• Unlike family member X-linked IAP (XIAP), which was predominantly cytoplasmic, the cIAP1 protein localized almost exclusively to nuclei in cells, as determined by immunofluorescence microscopy and subcellular fractionation methods [10].
• Expression of cIAP-1, cIAP-2, and XIAP, the most potent caspase inhibitors, was further investigated in three lung carcinoma cell lines after treatment with 8 Gy of ionizing radiation or etoposide (VP16) [21].
• In order to clarify the subcellular localization of cIAP-1 and to investigate its clinicopathological significance in head and neck SCCs (HNSCCs), we examined cIAP-1 expression in four oral SCC cell lines by immunocytochemistry and Western blot [22].
• Expression of cIAP1, a target for 11q22 amplification, correlates with resistance of cervical cancers to radiotherapy [23].
• DNA microarray assay suggested a decreased expression of genes encoding antiapoptotic proteins, cIAP1 and cIAP2, in the cells overexpressing IKKbeta-KM [24].

References