Disease relevance of Birc3

• During ischemia, IAP-2 is upregulated dramatically, while the other IAPs show little or no change [1].
• Overexpression of IAP-2 attenuates apoptosis and protects against myocardial ischemia/reperfusion injury in transgenic mice [1].
• We demonstrate here that cIAP2-/- mice exhibit profound resistance to lipopolysaccharide (LPS)-induced sepsis, specifically because of an attenuated inflammatory response [2].
• Here we report the striking induction by severe hypoxia of the anti-apoptotic protein IAP-2 [3].

High impact information on Birc3

• The cellular inhibitor of apoptosis 2 (cIAP2/HIAP1) is a potent inhibitor of apoptotic death [2].
• We show that LPS potently upregulates cIAP2 in macrophages and that cIAP2-/- macrophages are highly susceptible to apoptosis in a LPS-induced proinflammatory environment [2].
• Posttranscriptional downregulation of c-IAP2 by the ubiquitin protein ligase c-IAP1 in vivo [4].
• Transient transfection studies with wild-type and E3-defective c-IAP1 revealed that c-IAP2 is a direct target for c-IAP1-mediated ubiquitination and subsequent degradation, which are potentiated by the adaptor function of TRAF2 [4].
• Our results identify a novel translational regulatory mechanism that controls the expression of HIAP2 and point to the importance of tight regulation of antiapoptotic gene expression [5].

Biological context of Birc3

• Genomic and cDNA clones encoding mouse inhibitor of apoptosis protein 1 and 2 (Miap1 and Miap2) were isolated and characterized [6].
• The Miap1 gene consists of nine exons spanning 24 kb, and the Miap2 gene consists of seven exons spanning 21 kb [6].
• Fluorescence in situ hybridization analysis mapped the locus to chromosome 9A2, which is syntenic with portions of the human 11q22-q23 region containing the human homologues HIAP1 and HIAP2 [6].
• To test whether IAP-2 prevents cardiac apoptosis and injury following ischemia/reperfusion, we generated a line of transgenic mice that carried a mouse IAP-2 transgene [1].
• The translation of an antiapoptotic protein HIAP2 is regulated by an upstream open reading frame [5].

Anatomical context of Birc3

• Immunohistochemical studies revealed more intense staining of IAP-2 in the myocytes of transgenic mouse hearts [1].
• To assess the role of IAP-2 in I/R injury, the transgenic mice were subjected to ligation of the left descending anterior coronary artery ligation followed by reperfusion [1].
• Immunohistochemical localization of the IAPs in hOSE tumors demonstrated the presence of Xiap and Hiap-2, with their levels being highest in proliferative, but not apoptotic, epithelial cells [7].
• In situ hybridization showed that the expression of XIAP was remarkably reduced in the motor neurons of Tg mice, and the expression of cIAP-1 was strongly increased in the reactive astrocytes of Tg mice [8].
• Similarly, cIAP2 mRNA was induced by TNF-alpha in both H441 and A549 pulmonary epithelial cells but not in U937 cells [9].

Associations of Birc3 with chemical compounds

• Antisense down-regulation of X-linked inhibitor of apoptosis protein (Xiap), but not human inhibitor of apoptosis protein-2 (Hiap-2), induced apoptosis in cisplatin-sensitive and, to a lesser extent, in -resistant cells [7].
• On the other hand, IAP-2 induction was attenuated by actinomycin D, suggesting a role for gene transcription [3].
• Moreover, cobalt chloride and desferrioxamine activated HIF-1 but not IAP-2 [3].
• The loss of anti-apoptotic proteins Bcl-x(L) and inhibitor of apoptosis protein-2 (IAP-2) was also blocked by IL-7 [10].
• However, the ability of TNF-alpha to enhance IAP2 gene expression was significantly greater in TR than in C rats [11].

Other interactions of Birc3

• The X chromosome-linked inhibitor-of-apoptosis protein (XIAP) contributes to apoptosis regulation after a variety of cell death stimuli [12].

Analytical, diagnostic and therapeutic context of Birc3

• Sequence analysis of human, mouse and rat sequences revealed that there exists a short open reading frame (ORF) that is located just upstream of the HIAP2 coding sequence [5].
• DC2.4 were cultured with the pan-caspase inhibitor, ZVAD (100 micromol/L). cIAP, pro-caspases, and PARP expression or activation was measured by Western blot [13].
• Nuclear factor-kappaB activity was assessed by reporter gene assays and reverse transcriptase-polymerase chain reaction of the nuclear factor-kappaB dependent genes cIAP-2, Bfl/A1, and MnSOD [14].

References