Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Survivin is a novel member of the inhibitor of apoptosis protein (IAP) family, which is known to be over-expressed in various carcinomas and associated with their biologically aggressive characteristics. The aim of this study was to investigate survivin expression in human medullary thyroid carcinoma (MTC) and a MTC cell line TT, correlate survivin expression with clinicopathologic features of MTC, and test effects of antisurvivin oligonucleotides (ASODNs) on growth and apoptosis of TT cells. Survivin expression was immunohistochemically determined in formalin-fixed and paraffin-embedded specimens obtained from 10 cases of normal thyroid (NT) and 10 cases of MTC, and in TT cells. In TT cells, we confirmed survivin expression and its down-regulation by ASODNs using RT-PCR and Western blot analyses, and investigated effects of ASODNs on viability and growth by MTT assay and apoptosis by apoptotic analyses including DNA laddering assay, acridine orange/ethidium bromide staining and flow cytometric cell cycle analysis. Immunohistochemical analysis showed high survivin expression in MTC and TT cells, whereas no immunoreactivity was detectable in NT. Statistical analyses revealed no significant correlation of survivin expression with the clinicopathologic features of MTC. In TT cells, survivin expression at both mRNA and protein levels was confirmed and could be down-regulated by ASODNs concomitant with decrease in viability and growth, and increase in apoptosis. Our results suggest that survivin plays an important role in MTC independent of the conventional clinicopathologic factors, and ASODNs is a promising survivin-targeted gene therapy for MTC.
Exp Mol Med 2006 Jun 30
PMID:Antisurvivin oligonucleotides inhibit growth and induce apoptosis in human medullary thyroid carcinoma cells. 1681 81

The founding member of the inhibitor of apoptosis protein (IAP) family was originally identified as a cell death inhibitor. However, recent evidence suggests that IAPs are multifunctional signaling devices that influence diverse biological processes. To investigate the in vivo function of Drosophila melanogaster IAP2, we have generated diap2 null alleles. diap2 mutant animals develop normally and are fully viable, suggesting that diap2 is dispensable for proper development. However, these animals were acutely sensitive to infection by gram-negative bacteria. In Drosophila, infection by gram-negative bacteria triggers the innate immune response by activating the immune deficiency (imd) signaling cascade, a NF-kappaB-dependent pathway that shares striking similarities with the pathway of mammalian tumor necrosis factor receptor 1 (TNFR1). diap2 mutant flies failed to activate NF-kappaB-mediated expression of antibacterial peptide genes and, consequently, rapidly succumbed to bacterial infection. Our genetic epistasis analysis places diap2 downstream of or in parallel to imd, Dredd, Tak1, and Relish. Therefore, DIAP2 functions in the host immune response to gram-negative bacteria. In contrast, we find that the Drosophila TNFR-associated factor (Traf) family member Traf2 is dispensable in resistance to gram-negative bacterial infection. Taken together, our genetic data identify DIAP2 as an essential component of the Imd signaling cascade, protecting the organism from infiltrating microbes.
Mol Cell Biol 2006 Nov
PMID:The Drosophila inhibitor of apoptosis protein DIAP2 functions in innate immunity and is essential to resist gram-negative bacterial infection. 1689 30

For the bovine preimplantation embryo, insulin-like growth factor-I (IGF-I) is a survival factor that blocks the induction of apoptosis and reduces the decrease in development caused by heat shock. The first objective was to determine the signaling pathways whereby IGF-I acts to increase embryo cell number while inhibiting heat-shock induced apoptosis. Exposure of embryos to heat shock reduced cell number and increased percent apoptosis, but IGF-I increased cell number and blocked induction of apoptosis caused by heat shock. Actions of IGF-I to increase cell number were blocked by treatment with the mitogen activated protein kinase kinase (MAPKK) inhibitor PD 98059 whereas the phosphatidylinositol 3-kinase (PI3K) inhibitor LY 294002 had no effect. Conversely, LY 294002 but not PD 98059 blocked actions of IGF-I to inhibit induction of apoptosis caused by heat shock. The second objective was to determine whether IGF-I blocks effects of heat shock on development to the blastocyst stage by preventing apoptosis. Culture of embryos with IGF-I was effective in blocking the reduction in blastocyst development caused by heat shock-this action occurred even in the presence of LY 294002. Addition of another inhibitor of apoptosis, the caspase-3 inhibitor z-DEVD-fmk, did not mimic the protective effects of IGF-I on blastocyst development. Surprisingly, IGF-I was not effective in blocking the reduction in blastocyst development caused by heat shock when cultured with z-DEVD-fmk. In conclusion, the anti-apoptotic actions of IGF-I require PI3K signaling while actions to promote proliferation require MAPKK signaling. Moreover, actions of IGF-I to allow heat-shocked embryos to continue development to the blastocyst stage are independent of its anti-apoptotic effects.
Mol Reprod Dev 2007 Feb
PMID:Insulin-like growth factor-I promotes resistance of bovine preimplantation embryos to heat shock through actions independent of its anti-apoptotic actions requiring PI3K signaling. 1695 4

The Ras inhibitor farnesylthiosalicylic acid (FTS) has been shown to induce apoptosis in glioblastoma multiforme, but its mechanism of action was unknown. We show that FTS or dominant-negative Ras, by deregulating extracellular signal-regulated kinase and Akt signaling, decreases survivin gene transcripts in U87 glioblastoma multiforme, leading to disappearance of survivin protein and cell death. FTS affected both Ras-controlled regulators of survivin transcription and Ras-regulated survival signals. Thus, Ras inhibition by FTS resulted in release of the survivin "brake" on apoptosis and in activation of the mitochondrial apoptotic pathway: dephosphorylation of Bad, activation of Bax, release of cytochrome c, and caspase activation. FTS-induced apoptosis of U87 cells was strongly attenuated by forced expression of survivin or by caspase inhibitors. These results show that resistance to apoptosis in glioblastoma multiforme can be abolished by a single Ras inhibitor, which targets both survivin, a critical inhibitor of apoptosis, and the intrinsic mitochondrial apoptotic machinery.
Mol Cancer Ther 2006 Sep
PMID:Suppression of survivin expression in glioblastoma cells by the Ras inhibitor farnesylthiosalicylic acid promotes caspase-dependent apoptosis. 1698 68

The identification of differentially regulated apoptotic signals in normal and tumor cells allows the development of cancer cell-selective therapies. Increasing evidence shows that the inhibitor of apoptosis (IAP) proteins survivin and XIAP are highly expressed in tumor cells but are absent or have very low levels of expression in normal adult tissues. We found that inhibiting AKT activity with 10 to 100 nM deguelin, a small molecule derived from natural products, markedly reduced the levels of both survivin and XIAP, inducing apoptosis in human breast cancer cells but not in normal cells. It is noteworthy that we detected an elevated level of cleaved poly(ADP-ribose) polymerase, a signature of caspase activation, without a significant increase in caspase activity in deguelin-treated cancer cells. Our results suggest that severe down-regulation of the IAPs by deguelin releases their inhibitory activity over pre-existing active caspases present in cancer cells, inducing apoptosis without the need for further caspase activation. Because normal cells have very low levels of p-AKT, XIAP, survivin, and pre-existing caspase activity, deguelin had little effect on those cells. In addition, we found that combining deguelin with chemotherapy drugs enhanced drug-induced apoptosis selectively in human tumor cells, which suggests that deguelin has great potential for chemosensitization and could represent a new therapeutic agent for treatment of breast cancer.
Mol Pharmacol 2007 Jan
PMID:Down-regulation of inhibitor of apoptosis proteins by deguelin selectively induces apoptosis in breast cancer cells. 1703 97

Survivin is one of the 8 members of human inhibitor of apoptosis , which is differentially expressed in cancerous/transformed cells versus normal differentiated tissues. This retrospective study of thyroid histologic samples aimed to assess the clinical usefulness of survivin immunostaining for discrimination between follicular adenoma and carcinoma of thyroid. Immunohistochemical staining for survivin was performed on 41 lesions from patients who had undergone surgery for either follicular adenoma or carcinoma of thyroid. Survivin expression was significantly (P < 0.005) higher in the cases that received a diagnosis of carcinoma in comparison with follicular adenomas cases. Odds ratio of follicular carcinoma for survivin expression was 21.375 (95% CI: 3.283 to 139.177). Our results showed potential value of survivin in discrimination between follicular thyroid adenoma and follicular thyroid carcinoma. We conclude that survivin is a potential candidate for further investigation in the proper histologic diagnosis of thyroid cancers.
Appl Immunohistochem Mol Morphol 2006 Dec
PMID:Immunohistochemical analysis of survivin expression in thyroid follicular adenoma and carcinoma. 1712 39

Vascular remodeling and atheromatous lesion formation are determined in part by the balance between apoptosis and survival of vascular smooth muscle cells (VSMCs). In the chronic stages, apoptosis of VSMCs in the atherosclerotic plaques contributes to the weakening and potential rupture of the plaque causing pathologies such as acute coronary syndrome. The higher incidence of apoptosis in the plaques of symptomatic than in asymptomatic patients has been demonstrated, but the expression of survival proteins, including the inhibitor of apoptosis proteins (IAPs), has not been thoroughly examined. The aim of this study was to investigate the immunohistochemical expression of cellular inhibitor of apoptosis protein-2 (cIAP2), x-linked inhibitor of apoptosis protein (XIAP), and survivin in normal carotid arteries, and carotid endarterectomy specimens of symptomatic and asymptomatic patients with carotid stenosis. The results demonstrated stronger immunopositivity to smooth muscle myosin heavy chain antigen (SM-MHC) (sm2), proliferating cell nuclear antigen (PCNA), and p50 subunit of NF-kappabeta in the asymptomatic plaques than in symptomatic plaques. Furthermore, there was higher expression of cIAP2, XIAP, and survivin in the symptomatic than in the asymptomatic plaques and this paralleled caspase-3 expression. The increased expression of IAPs in symptomatic plaques could be due to endogenous defense mechanism to protect against the pro-apoptotic effect of the inflammatory stimuli that are released in the plaques. This could be involved in the stabilization of symptomatic atheromatous plaques and may prove a potential therapeutic target.
Exp Mol Pathol 2007 Aug
PMID:Increased expression of inhibitor of apoptosis proteins in atherosclerotic plaques of symptomatic patients with carotid stenosis. 1720 24

Livin, also called melanoma inhibitor of apoptosis protein (IAP) or kidney IAP, is a member of the IAP family of caspase inhibitors that selectively binds the endogenous IAP antagonist SMAC and caspase-3, caspase-7, and caspase-9. As such, Livin inhibits apoptosis, and its overexpression renders malignant cells resistant to chemotherapy. Therefore, inhibitors of Livin could be useful adjuncts to chemotherapy in the treatment of malignancies. This review will discuss Livin as a potential therapeutic target and strategies for its inhibition, including antisense oligonucleotides, small-molecule inhibitors, and immune-mediated approaches.
Mol Cancer Ther 2007 Jan
PMID:Livin/melanoma inhibitor of apoptosis protein as a potential therapeutic target for the treatment of malignancy. 1723 63

To identify cancer-specific targets, we have conducted a synthetic lethal screen using a small interfering RNA (siRNA) library targeting approximately 4,000 individual genes for enhanced killing in the DLD-1 colon carcinoma cell line that expresses an activated copy of the K-Ras oncogene. We found that siRNAs targeting baculoviral inhibitor of apoptosis repeat-containing 5 (survivin) significantly reduced the survival of activated K-Ras-transformed cells compared with its normal isogenic counterpart in which the mutant K-Ras gene had been disrupted (DKS-8). In addition, survivin siRNA induced a transient G(2)-M arrest and marked polyploidy that was associated with increased caspase-3 activation in the activated K-Ras cells. These results indicate that tumors expressing the activated K-Ras oncogene may be particularly sensitive to inhibitors of the survivin protein.
Mol Cancer Ther 2007 Jan
PMID:Survivin depletion preferentially reduces the survival of activated K-Ras-transformed cells. 1723 86

We sequenced and characterized the inhibitor of apoptosis (iap) 1 gene from Aedes albopictus, designated as Aaiap1. The Aaiap1 gene rescued Spodoptera frugiperda (Sf9) cells from apoptosis when cotransfected with the Drosophila pro-apoptotic hid gene. The antiapoptotic function of the Aaiap1 gene was evaluated in the bluetongue virus (BTV)-induced apoptosis system. BTV infection induced apoptosis in vertebrate cells via the intrinsic apoptotic pathway. This was shown by the translocation of cytochrome C and the second mitochondria-derived activator of caspase (Smac, also known as DIABLO) from the mitochondria and the subsequent activation of caspase-9 and -3. Stable expression of the Aaiap1 gene in derivative baby hamster kidney cells delayed BTV-induced apoptosis by 24 h and reduced the BTV progeny yield by 10-fold. This study provides the first evidence that the mosquito AaIAP1 protein possesses antiapoptotic activity.
Insect Mol Biol 2007 Feb
PMID:The Aedes albopictus inhibitor of apoptosis 1 gene protects vertebrate cells from bluetongue virus-induced apoptosis. 1725 12


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>