Disease relevance of Birc4

• However, the interaction among XIAP, Smac/DIABLO, and caspases after in vivo cerebral ischemia is not well known [1].
• Altogether, these data define a powerful survival function for XIAP and reinforce its possible role as a therapeutic target in human glioma cells.Gene Therapy (2007) 14, 147-161. doi:10.1038/sj.gt.3302845; published online 7 September 2006 [2].
• XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer [3].
• We explored the expression of Smac/DIABLO, a newly identified mitochondrial apoptogenic molecule, and X-linked inhibitor of apoptosis protein (XIAP) in the brain subjected to ischemia/reperfusion [4].
• When expressed in spinal motor neurons of mutant SOD1 mice using transgenic techniques, XIAP attenuated disease progression without delaying onset [5].

High impact information on Birc4

• The c-IAP1 and XIAP inhibitors of apoptosis were selectively lost in glucocorticoid- or etoposide-treated thymocytes in a proteasome-dependent manner before death [6].
• A new internal-ribosome-entry-site motif potentiates XIAP-mediated cytoprotection [7].
• Furthermore, concomitant expression of Pin1 and HBx in the nontumorigenic human hepatocyte cell line MIHA led to a synergistic increase in tumor growth [8].
• A novel role for XIAP in copper homeostasis through regulation of MURR1 [9].
• XIAP is a potent suppressor of apoptosis that directly inhibits specific members of the caspase family of cysteine proteases [9].

Chemical compound and disease context of Birc4

• FTY720 selectively induced cell apoptosis in hepatoma cell lines with overexpression of cleaved caspase-3 and caspase-9, but the same phenomena were not found in MIHA cells [10].

Biological context of Birc4

• Adenoviral expression of XIAP antisense RNA induces apoptosis in glioma cells and suppresses the growth of xenografts in nude mice [2].
• XIAP inhibits the caspase reaction via binding to caspases, and is inhibited via binding to the second mitochondria-derived activator of caspase (Smac)/DIABLO to tightly control apoptotic cell death [1].
• Northern blot analysis reveals an 8-kb miap-3 transcript in all tissues examined to date. miap-3 is composed of six exons and five introns spanning approximately 20 kb. miap-3 has been assigned to the A3-A5 region of mouse chromosome X by FISH analysis [11].
• Results from 3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide and clonogenic assays suggest that inhibition of survivin or XIAP greatly decreased cell survival following irradiation [3].
• This suggests that there exists a compensatory mechanism that leads to upregulation of other family members when XIAP expression is lost [12].

Anatomical context of Birc4

• In contrast, non-neoplastic SV-FHAS human astrocytes and other non-neoplastic cells express XIAP at very low levels and resist these effects of adenovirus-expressing XIAP antisense RNA (Ad-XIAP-as) [2].
• 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 [13].
• XIAP-deficiency leads to delayed lobuloalveolar development in the mammary gland [14].
• Conversely, adenovirally-mediated overexpression of NAIP or the X-linked IAP called XIAP reduces the loss of CA1 hippocampal neurons following transient forebrain ischemia [15].
• To study the role of this, we generated double transgenic mice expressing XIAP in ALS spinal cord neurons using the Thy1 promoter [16].

Associations of Birc4 with chemical compounds

• Sequential treatment with SN-38 followed by flavopiridol was associated with higher activation of caspase-3 and greater cleavage of both p21 and XIAP, an inhibitor of apoptosis, compared with other treatment schedules [17].
• These results suggest that the ability of cisplatin to down-regulate Xiap content may be an important determinant of chemosensitivity in hOSE cancer [18].
• Furthermore, NSE-xiap mice treated with MPTP did not exhibit deficits in exploratory behaviour in an open-field test [19].
• We demonstrate that nigrostriatal dopamine neurons of NSE-xiap mice were resistant to the damaging effects of the dopaminergic neurotoxin MPTP [19].
• Finally, elevated expression of X-linked inhibitor of apoptosis, XIAP, was observed in thymi from DEX-treated PRL -/-Graft mice [20].

Regulatory relationships of Birc4

• In contrast, the neuronal competence pathway permitted cytochrome c to activate caspases by inducing a marked reduction in XIAP levels in these neurons [21].

Other interactions of Birc4

• To examine the relationship of the XIAP pathway to the caspase cascade, a pan-caspase inhibitor was administered [1].
• The X chromosome-linked inhibitor-of-apoptosis protein (XIAP) contributes to apoptosis regulation after a variety of cell death stimuli [1].
• The purpose of this study was to determine whether inhibition of survivin, XIAP, or both enhances radiotherapy in a lung cancer model [3].
• In addition, Sept4 mutant sperm showed defects in the elimination of residual cytoplasm during sperm maturation and had increased staining for the caspase inhibitor XIAP [22].
• In SNU251 cells expressing BRCA1(S1423/1524A), the inhibitory interaction between X-linked inhibitor of apoptosis protein (XIAP) and caspase-9 remains intact after UV, compared with cells expressing wt BRCA1 [23].

Analytical, diagnostic and therapeutic context of Birc4

• The subcellular localization of XIAP became more extensive within the cells during reperfusion, as compared with the normal state [4].
• To better understand the function of XIAP in normal cells, we generated mice deficient in XIAP through homologous gene targeting [12].
• The XIAP transgenic animals exhibited significantly smaller brain damage, as shown by TUNEL labelling, less reduction in brain protein synthesis, and less active caspase-3 after ischemia compared with controls [24].
• METHODS AND RESULTS: Western blot analysis revealed discrete survivin expression in human aorta lipid streaks but virtually none in advanced atherosclerotic plaques, despite increased XIAP and cIAP2 levels [25].
• Primary pancreatic cancers were assessed for XIAP expression by immunohistochemistry, using a pancreatic cancer tissue microarray [26].

References