Disease relevance of Birc5

• TIAP has one baculovirus IAP repeat and lacks a C-terminal RING finger motif [1].
• XIAP and survivin as therapeutic targets for radiation sensitization in preclinical models of lung cancer [2].
• Here, we found that survivin, a member of the apoptosis-inhibiting gene family, and aurora B kinase, a chromosomal passenger protein, were co-overexpressed in the various glioblastoma cell lines and tumors [3].
• Lentivirus-mediated gene therapy by suppressing survivin in BALB/c nude mice bearing oral squamous cell carcinoma [4].
• In order to establish the role of anti apoptotic proteins in colon cancer development, we studied with immunohistochemical techniques the expression of Survivin in a mouse model of colon carcinogenesis induced by 1,2-dimethyl-hydrazine treatment [5].

High impact information on Birc5

• Inhibitor of apoptosis protein survivin regulates vascular injury [6].
• Serum or PDGF-AB stimulated survivin expression in cultured smooth-muscle cells (SMCs), which suppressed apoptosis and prevented caspase activation [6].
• Here we show that a new inhibitor of apoptosis (IAP) protein, survivin, is expressed in the G2/M phase of the cell cycle in a cycle-regulated manner [7].
• The overexpression of survivin in cancer may overcome this apoptotic checkpoint and favour aberrant progression of transformed cells through mitosis [7].
• At the beginning of mitosis, survivin associates with microtubules of the mitotic spindle in a specific and saturable reaction that is regulated by microtubule dynamics [7].

Chemical compound and disease context of Birc5

• Expression of a phosphorylation-defective survivin mutant (Thr(34)-->Ala) triggered apoptosis in several human melanoma cell lines and enhanced cell death induced by the chemotherapeutic drug cisplatin in vitro [8].
• Plasmid constructs expressing survivin antisense and DN mutant replacing the cysteine residue at amino acid 84 with alanine (Cys84Ala) were prepared and introduced into BCG-823 and MKN-45 gastric cancer cells to establish stable transfectants [9].
• We decided to evaluate the effects of a ribozyme-based strategy for survivin inhibition in androgen-independent human prostate cancer cells [10].
• METHODS: A semiautomatic 3-dimensional algorithm was used to delineate the LV myocardial wall on static PET images depicting myocardial glucose metabolism ((18)F-FDG PET) for 20 mice: 10 wild-type and 10 genetically modified littermates designed to develop a dilative cardiomyopathy phenotype (cardiomyocyte-specific knockout of survivin) [11].
• Our study, for the first time, demonstrated that 1) resveratrol imparts strong chemopreventive effects against UVB exposure-mediated skin carcinogenesis (relevant to human skin cancers), and 2) the chemopreventive effects of resveratrol may, at least in part, be mediated via modulations in Survivin and other associated events [12].

Biological context of Birc5

• Moreover, Survivin expression alone is sufficient to restore proliferation and to antagonize apoptosis in costimulation-deficient T cells and can rescue T cell expansion in vivo [13].
• In in vitro studies, TIAP was induced in splenic T cells activated with anti-CD3 antibody or Con A, and the expression of TIAP was up-regulated in synchronized NIH 3T3 cells at S to G2/M phase of the cell cycle [1].
• We propose that during cell proliferation, cellular protective activity may be augmented with inducible IAPs such as TIAP [1].
• Furthermore, modulating Survivin expression increased polyploidy in c-kit+, Lin- cells, which was accentuated by p21 deficiency [14].
• Survivin is a cancer gene implicated in inhibition of apoptosis and regulation of mitosis, but its function in normal cells has remained elusive [15].

Anatomical context of Birc5

• Thus, sustained Survivin expression from costimulatory signaling maintains T cell division over time and regulates the extent of clonal expansion [13].
• Histological examinations revealed that TIAP is expressed in growing tissues such as thymus, testis, and intestine of adult mice and many tissues of embryos [1].
• The cyclin-dependent kinase inhibitor p21WAF1/Cip1 and Survivin enhance granulocyte macrophage colony-forming unit (CFU-GM) cell cycle and proliferation and have been implicated as antiapoptotic proteins [14].
• Here, we show that transgenic mice expressing survivin in pancreatic islet beta-cells show no changes in cell proliferation, as determined by islet size or islet number [15].
• Previously, we demonstrated that survivin (also known as BIRC5), an anti-apoptotic gene expressed in mouse preimplantation embryos, protects embryos from apoptosis [16].

Associations of Birc5 with chemical compounds

• Tetra-O-methyl nordihydroguaiaretic acid induces growth arrest and cellular apoptosis by inhibiting Cdc2 and survivin expression [17].
• This down-regulation does not result from transcriptional changes, as determined by quantitative real-time PCR, but cycloheximide treatment indicates that survivin half-life is reduced from 6 to 2 h, which is secondary to ubiquitination and proteasomal degradation [18].
• Relative to SAHA, (S)-HDAC-42 exhibited distinctly superior apoptogenic potency, and caused markedly greater decreases in phospho-Akt, Bcl-xL, and survivin in PC-3 cells [19].
• Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections by using polyclonal antibody ab469 for survivin, and mouse monoclonal antibodies (clone 124 and DO-7), for bcl-2 and p53, respectively [20].
• Therefore, we investigated the expression of survivin in a murine liver regeneration model after partial hepatectomy and intraperitoneal carbon tetrachloride (CCl(4)) injection [21].

Regulatory relationships of Birc5

• Survivin is induced by OX40 independent of mitotic progression in late G1, and blocking Survivin suppresses S-phase transition and division of T cells and leads to apoptosis [13].
• Thus, TGFA inhibits apoptosis in mouse blastocysts through upregulation of survivin expression via the PI3K pathway [16].
• Strikingly, loss of survivin activates the tumor suppressor p53 [22].
• ICG-001-mediated downregulation of survivin expression enhanced caspase-3 activity and apoptosis, which was rescued by overexpression of wild type but not mutant (C84A) survivin [23].
• Transfection of ovarian carcinoma cells with Ad Survivin T34A induces apoptosis via a caspase 9-mediated pathway that is not affected by cell cycle block prior to G2/M [24].

Other interactions of Birc5

• Sustained survivin expression from OX40 costimulatory signals drives T cell clonal expansion [13].
• Using an antisense approach, we examined whether upregulation of survivin is responsible for the anti-apoptotic effect of TGFA in blastocysts [16].
• Survivin allows effector T cells to accumulate in large numbers, but Bcl-2 family proteins are required for T cell survival after the phase of active division [13].
• Here, we show that Survivin is controlled in peripheral T cells by OX40 cosignaling via sustained PI3k and PKB activation [13].
• Deficiency of survivin in transgenic mice exacerbates Fas-induced apoptosis via mitochondrial pathways [25].

Analytical, diagnostic and therapeutic context of Birc5

• These broad cytoprotective functions of survivin in vivo might be beneficial for gene therapy of diabetes [15].
• Transplantation of survivin transgenic islets in diabetic recipient mice affords long-term engraftment and stable correction of hyperglycaemia [15].
• Tumor growth in mice treated with ASO (50 and 75 mg/kg per day) was significantly inhibited (45.31% and 60.94%, respectively) compared with saline-injected group (p < 0.01), in a dose-dependent manner, and the effect of ASO on tumor growth was associated with downregulation of survivin in tumor xenografts [26].
• Intraperitoneal injection of low-dose Jo2 had no effect on survivin+/+ mice at 2 hours [25].
• The purpose of this study was to determine whether inhibition of survivin, XIAP, or both enhances radiotherapy in a lung cancer model [2].

References