存活素(survivin)為抗細胞凋亡蛋白質(IAP)家族的一員，存活素與其他家族成員的不同之處在於其只會在胚胎和癌症組織中表達，但是不在成熟和已分化的組織中表達，此外存活素的過渡表達(overexpression)與癌症的進程及抗藥性息息相關，雖然存活素被認為是一個很好的癌症治療標靶，但其仍然被認為是一個semi-druggable的蛋白質，在近十年研究中僅有少數的專一性存活素抑制劑被開發，其中只有一個藥物-YM155進入臨床第二期的測試，不幸的，在近期的研究發現YM155是多重抗藥性蛋白質(MDR-1)的受質，此研究可能限制YM155在臨床的應用，因此開發新穎的專一性存活素抑制劑是非常迫切的。本研究的目的在於探討不同的dominant-negative 存活素的抗癌效果的分子機制和開發一個新穎的可以應用在臨床癌症治療且可以口服的專一性存活素抑制劑，其中包裹具有細胞通透性的dominant-negative存活素的奈米微粒。在MTT細胞存活率及西方點墨法的實驗中我們發現 T34A/C84A (雙突變)的dominant-negative存活素的抑制癌症生長的效果比T34A和C84A （單一突變）好。在進行蛋白質純化之前，本研究先建構具有細胞通透性的dominant-negative存活素的質體DNA，且在T34A/C84A存活素的N端接上GST及在C端接上9個精胺酸 (arginine)。而本研究利用大腸桿菌 BL21(DE3) codon plus RIPL表達dominant-negative存活素蛋白質，而為了增加所表達的非水溶的dominant-negative存活素蛋白質的水溶性，本研究調整誘導時的溫度和IPTG的濃度及表達的時間以及lysis buffer的配方。最後我們利用GST親和性層析法以及陽離子交換樹脂層析法將水溶性的dominant-negative存活素蛋白質純化，從SDS-PAGE和西方點墨法的實驗結果中得知我們在適當的條件下成功的將dominant-negative存活素蛋白質純化。而在包裹成奈米微粒前dominant-negative存活素蛋白質的治療癌症效果將會被進一步的探討。

Survivin is a member of the inhibitor-of-apoptosis (IAP) family. Unlike other family members, survivin is primarily expressed in fetal and cancerous tissue rather than in differentiated adult tissue. Overexpression of survivin is correlated with poor prognosis and drug resistance in cancer patients. Although survivin has been proposed as a promising molecular target for cancer treatment, it is widely believed that survivin is only a semi-druggable target. In fact, only a few survivin inhibitors have been developed and only one survivin specific small molecular inhibitor, YM155, has successfully reached phase II clinical trials in the past decade. Unfortunately, recently studies demonstrated that YM155 is a substrate of the multiple-drug resistant protein (MDR-1), and this property actually limits its clinical potential. Therefore, it is quite urgent to develop a new survivin specific inhibitor. The aim of this study is to evaluate the molecular mechanism of anti-cancer effects of various dominant-negative survivin mutants and to develop a novel oral and clinical applicable survivin specific macromolecular inhibitor, a cell permeable dominant-negative survivin protein loaded nanoparticles, for the treatment of cancer. MTT cell viability and Western blot analysis revealed that the T34A/C84A (double point mutation) dominant-negative survivin exhibits higher anti-cancer effects as compared to both T34A and C84A (single point mutation) dominant-negative survivin in vitro. A cell-permeable dominant-negative form of survivin (GST-tagged dNSurR9-T34A/C84A) comprising a N-terminal GST-tag and nine C-terminal arginine residues fused to the T34A/C84A dominant-negative survivin mutant was constructed. The GST-tagged recombinant survivin protein was expressed using bacteria [E. coli BL21(DE3) codon plus RIPL strain] protein expression system. The expressed insoluble GST-tagged dNSurR9-T34A/C84A proteins were solubilized by varying the induction temperatures, IPTG concentrations, expression durations and lysis buffer compositions. The solubilized recombinant proteins were purified using the GST affinity chromatography and cation-exchange chromatography. Results of the sodium dodecyl sulfate polyacrylamide gel electrophoresis and the Western blot analysis showed that the recombinant proteins was successfully solubilized and purified under the optimized conditions. Further studies are needed to determine the anti-cancer activity of the purified protein before nanoparticle encapsulations.

Adida, C., D. Berrebi, M. Peuchmaur, M. Reyes-Mugica, and D.C. Altieri. 1998. Anti-apoptosis gene, survivin, and prognosis of neuroblastoma. Lancet. 351:882-883.
Alarcon, T., and M.J. Tindall. 2007. Modelling cell growth and its modulation of the G1/S transition. Bulletin of mathematical biology. 69:197-214.
Albert, B., Bray, D., Lewis, J., Raff, M., Roberts, K., Wastson, J.D. 1994. Molecular Biology of the Cell, 2nd. New York and London: Garland Publishing Inc.
Ambrosini, G., C. Adida, and D.C. Altieri. 1997. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma. Nature medicine. 3:917-921.
Banks, D.P., J. Plescia, D.C. Altieri, J. Chen, S.H. Rosenberg, H. Zhang, and S.C. Ng. 2000. Survivin does not inhibit caspase-3 activity. Blood. 96:4002-4003.
Baneyx, F., and M. Mujacic. 2004. Recombinant protein folding and misfolding in Escherichia coli. Nature biotechnology. 22:1399-1408.
Barrett, R.M., T.P. Osborne, and S.P. Wheatley. 2009. Phosphorylation of survivin at threonine 34 inhibits its mitotic function and enhances its cytoprotective activity. Cell cycle. 8:278-283.
Beug, S.T., H.H. Cheung, E.C. LaCasse, and R.G. Korneluk. 2012. Modulation of immune signalling by inhibitors of apoptosis. Trends in immunology. 33:535-545.
Blanc-Brude, O.P., M. Mesri, N.R. Wall, J. Plescia, T. Dohi, and D.C. Altieri. 2003. Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis. Clinical cancer research : an official journal of the American Association for Cancer Research. 9:2683-2692.
Bolton, M.A., W. Lan, S.E. Powers, M.L. McCleland, J. Kuang, and P.T. Stukenberg. 2002. Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation. Molecular biology of the cell. 13:3064-3077.
Boran, T., H. Lesot, M. Peterka, and R. Peterkova. 2005. Increased apoptosis during morphogenesis of the lower cheek teeth in tabby/EDA mice. Journal of dental research. 84:228-233.
Bryksin, A.V., and I. Matsumura. 2010. Overlap extension PCR cloning: a simple and reliable way to create recombinant plasmids. BioTechniques. 48:463-465.
Carrasco, R.A., N.B. Stamm, E. Marcusson, G. Sandusky, P. Iversen, and B.K. Patel. 2011. Antisense inhibition of survivin expression as a cancer therapeutic. Molecular cancer therapeutics. 10:221-232.
Chantalat, L., D.A. Skoufias, J.P. Kleman, B. Jung, O. Dideberg, and R.L. Margolis. 2000. Crystal structure of human survivin reveals a bow tie-shaped dimer with two unusual alpha-helical extensions. Molecular cell. 6:183-189.
Cheng, Q., X. Ling, A. Haller, T. Nakahara, K. Yamanaka, A. Kita, H. Koutoku, M. Takeuchi, M.G. Brattain, and F. Li. 2012. Suppression of survivin promoter activity by YM155 involves disruption of Sp1-DNA interaction in the survivin core promoter. International journal of biochemistry and molecular biology. 3:179-197.
Cheung, C.H., C.C. Huang, F.Y. Tsai, J.Y. Lee, S.M. Cheng, Y.C. Chang, Y.C. Huang, S.H. Chen, and J.Y. Chang. 2013. Survivin - biology and potential as a therapeutic target in oncology. OncoTargets and therapy. 6:1453-1462.
Cheung, C.H., X. Sun, J.R. Kanwar, J.Z. Bai, L. Cheng, and G.W. Krissansen. 2010. A cell-permeable dominant-negative survivin protein induces apoptosis and sensitizes prostate cancer cells to TNF-alpha therapy. Cancer cell international. 10:36.
Coumar, M.S., F.Y. Tsai, J.R. Kanwar, S. Sarvagalla, and C.H. Cheung. 2013. Treat cancers by targeting survivin: just a dream or future reality? Cancer treatment reviews. 39:802-811.
Croci, D.O., I.S. Cogno, N.B. Vittar, E. Salvatierra, F. Trajtenberg, O.L. Podhajcer, E. Osinaga, G.A. Rabinovich, and V.A. Rivarola. 2008. Silencing survivin gene expression promotes apoptosis of human breast cancer cells through a caspase-independent pathway. Journal of cellular biochemistry. 105:381-390.
Deveraux, Q.L., and J.C. Reed. 1999. IAP family proteins--suppressors of apoptosis. Genes & development. 13:239-252.
Dogan, M., S. Cagli, I. Yuce, A. Bayram, M.A. Somdas, D. Karatas, M.C. Cihan, F. Yuksel, and E. Guney. 2014. Survivin expression correlates with nodal metastasis in T1-T2 squamous cell carcinoma of the tongue. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies.
Dohi, T., K. Okada, F. Xia, C.E. Wilford, T. Samuel, K. Welsh, H. Marusawa, H. Zou, R. Armstrong, S. Matsuzawa, G.S. Salvesen, J.C. Reed, and D.C. Altieri. 2004. An IAP-IAP complex inhibits apoptosis. The Journal of biological chemistry. 279:34087-34090.
Esposito, I., J. Kleeff, I. Abiatari, X. Shi, N. Giese, F. Bergmann, W. Roth, H. Friess, and P. Schirmacher. 2007. Overexpression of cellular inhibitor of apoptosis protein 2 is an early event in the progression of pancreatic cancer. Journal of clinical pathology. 60:885-895.
Ferrer, M., T.N. Chernikova, M.M. Yakimov, P.N. Golyshin, and K.N. Timmis. 2003. Chaperonins govern growth of Escherichia coli at low temperatures. Nature biotechnology. 21:1266-1267.
Fink, S.L., and B.T. Cookson. 2005. Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infection and immunity. 73:1907-1916.
Frankel, S., R. Sohn, and L. Leinwand. 1991. The use of sarkosyl in generating soluble protein after bacterial expression. Proceedings of the National Academy of Sciences of the United States of America. 88:1192-1196.
Fukuda, S., and L.M. Pelus. 2004. Activated H-Ras regulates hematopoietic cell survival by modulating Survivin. Biochemical and biophysical research communications. 323:636-644.
Hahm, E.R., and S.V. Singh. 2007. Honokiol causes G0-G1 phase cell cycle arrest in human prostate cancer cells in association with suppression of retinoblastoma protein level/phosphorylation and inhibition of E2F1 transcriptional activity. Molecular cancer therapeutics. 6:2686-2695.
He, S.Q., H. Rehman, M.G. Gong, Y.Z. Zhao, Z.Y. Huang, C.H. Li, W.G. Zhang, and X.P. Chen. 2007. Inhibiting survivin expression enhances TRAIL-induced tumoricidal activity in human hepatocellular carcinoma via cell cycle arrest. Cancer biology & therapy. 6:1247-1257.
Hengartner, M.O. 2000. The biochemistry of apoptosis. Nature. 407:770-776.
Herrington, W.G., D.C. Talbot, M.M. Lahn, J.T. Brandt, S. Callies, R. Nagle, C.G. Winearls, and I.S. Roberts. 2011. Association of long-term administration of the survivin mRNA-targeted antisense oligonucleotide LY2181308 with reversible kidney injury in a patient with metastatic melanoma. American journal of kidney diseases : the official journal of the National Kidney Foundation. 57:300-303.
Holcik, M., and R.G. Korneluk. 2001. XIAP, the guardian angel. Nature reviews. Molecular cell biology. 2:550-556.
Hu, Q., W. Li, X. Hu, Q. Hu, J. Shen, X. Jin, J. Zhou, G. Tang, and P.K. Chu. 2012. Synergistic treatment of ovarian cancer by co-delivery of survivin shRNA and paclitaxel via supramolecular micellar assembly. Biomaterials. 33:6580-6591.
Huang, Y., R.L. Rich, D.G. Myszka, and H. Wu. 2003. Requirement of both the second and third BIR domains for the relief of X-linked inhibitor of apoptosis protein (XIAP)-mediated caspase inhibition by Smac. The Journal of biological chemistry. 278:49517-49522.
Hwang, P.M., J.S. Pan, and B.D. Sykes. 2014. Targeted expression, purification, and cleavage of fusion proteins from inclusion bodies in Escherichia coli. FEBS letters. 588:247-252.
Islam, A., H. Kageyama, K. Hashizume, Y. Kaneko, and A. Nakagawara. 2000a. Role of survivin, whose gene is mapped to 17q25, in human neuroblastoma and identification of a novel dominant-negative isoform, survivin-beta/2B. Medical and pediatric oncology. 35:550-553.
Islam, A., H. Kageyama, N. Takada, T. Kawamoto, H. Takayasu, E. Isogai, M. Ohira, K. Hashizume, H. Kobayashi, Y. Kaneko, and A. Nakagawara. 2000b. High expression of Survivin, mapped to 17q25, is significantly associated with poor prognostic factors and promotes cell survival in human neuroblastoma. Oncogene. 19:617-623.
Iwai, M., T. Minematsu, Q. Li, T. Iwatsubo, and T. Usui. 2011. Utility of P-glycoprotein and organic cation transporter 1 double-transfected LLC-PK1 cells for studying the interaction of YM155 monobromide, novel small-molecule survivin suppressant, with P-glycoprotein. Drug metabolism and disposition: the biological fate of chemicals. 39:2314-2320.
Jeyaprakash, A.A., C. Basquin, U. Jayachandran, and E. Conti. 2011. Structural basis for the recognition of phosphorylated histone h3 by the survivin subunit of the chromosomal passenger complex. Structure. 19:1625-1634.
Jeyaprakash, A.A., U.R. Klein, D. Lindner, J. Ebert, E.A. Nigg, and E. Conti. 2007. Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together. Cell. 131:271-285.
Jiang, X., C. Wilford, S. Duensing, K. Munger, G. Jones, and D. Jones. 2001. Participation of Survivin in mitotic and apoptotic activities of normal and tumor-derived cells. Journal of cellular biochemistry. 83:342-354.
Johnson, M.E., and E.W. Howerth. 2004. Survivin: a bifunctional inhibitor of apoptosis protein. Veterinary pathology. 41:599-607.
Kanduc, D., A. Mittelman, R. Serpico, E. Sinigaglia, A.A. Sinha, C. Natale, R. Santacroce, M.G. Di Corcia, A. Lucchese, L. Dini, P. Pani, S. Santacroce, S. Simone, R. Bucci, and E. Farber. 2002. Cell death: apoptosis versus necrosis (review). International journal of oncology. 21:165-170.
Kawasaki, H., D.C. Altieri, C.D. Lu, M. Toyoda, T. Tenjo, and N. Tanigawa. 1998. Inhibition of apoptosis by survivin predicts shorter survival rates in colorectal cancer. Cancer research. 58:5071-5074.
Kelly, A.E., C. Ghenoiu, J.Z. Xue, C. Zierhut, H. Kimura, and H. Funabiki. 2010. Survivin reads phosphorylated histone H3 threonine 3 to activate the mitotic kinase Aurora B. Science. 330:235-239.
Khan, S., J.R. Aspe, M.G. Asumen, F. Almaguel, O. Odumosu, S. Acevedo-Martinez, M. De Leon, W.H. Langridge, and N.R. Wall. 2009a. Extracellular, cell-permeable survivin inhibits apoptosis while promoting proliferative and metastatic potential. British journal of cancer. 100:1073-1086.
Khan, Z., R.P. Tiwari, R. Mulherkar, N.K. Sah, G.B. Prasad, B.R. Shrivastava, and P.S. Bisen. 2009b. Detection of survivin and p53 in human oral cancer: correlation with clinicopathologic findings. Head & neck. 31:1039-1048.
Kim, S.K., and L. Huang. 2012. Nanoparticle delivery of a peptide targeting EGFR signaling. Journal of controlled release : official journal of the Controlled Release Society. 157:279-286.
Kita, A., T. Nakahara, K. Yamanaka, K. Nakano, M. Nakata, M. Mori, N. Kaneko, H. Koutoku, N. Izumisawa, and M. Sasamata. 2011. Antitumor effects of YM155, a novel survivin suppressant, against human aggressive non-Hodgkin lymphoma. Leukemia research. 35:787-792.
Kobayashi, K., M. Hatano, M. Otaki, T. Ogasawara, and T. Tokuhisa. 1999. Expression of a murine homologue of the inhibitor of apoptosis protein is related to cell proliferation. Proceedings of the National Academy of Sciences of the United States of America. 96:1457-1462.
Lang, R.A. 1997. Apoptosis in mammalian eye development: lens morphogenesis, vascular regression and immune privilege. Cell death and differentiation. 4:12-20.
Lechler, P., X. Wu, W. Bernhardt, V. Campean, S. Gastiger, T. Hackenbeck, B. Klanke, A. Weidemann, C. Warnecke, K. Amann, D. Engehausen, C. Willam, K.U. Eckardt, F. Rodel, and M.S. Wiesener. 2007. The tumor gene survivin is highly expressed in adult renal tubular cells: implications for a pathophysiological role in the kidney. The American journal of pathology. 171:1483-1498.
Leung, E., N. Kannan, G.W. Krissansen, M.P. Findlay, and B.C. Baguley. 2010. MCF-7 breast cancer cells selected for tamoxifen resistance acquire new phenotypes differing in DNA content, phospho-HER2 and PAX2 expression, and rapamycin sensitivity. Cancer biology & therapy. 9:717-724
Lewis, K.D., W. Samlowski, J. Ward, J. Catlett, L. Cranmer, J. Kirkwood, D. Lawson, E. Whitman, and R. Gonzalez. 2011. A multi-center phase II evaluation of the small molecule survivin suppressor YM155 in patients with unresectable stage III or IV melanoma. Investigational new drugs. 29:161-166.
Li, C., Z. Wu, M. Liu, M. Pazgier, and W. Lu. 2008. Chemically synthesized human survivin does not inhibit caspase-3. Protein science : a publication of the Protein Society. 17:1624-1629.
Li, F., and D.C. Altieri. 1999. The cancer antiapoptosis mouse survivin gene: characterization of locus and transcriptional requirements of basal and cell cycle-dependent expression. Cancer research. 59:3143-3151.
Li, F., G. Ambrosini, E.Y. Chu, J. Plescia, S. Tognin, P.C. Marchisio, and D.C. Altieri. 1998. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 396:580-584.
Li, F., and X. Ling. 2006. Survivin study: an update of "what is the next wave"? Journal of cellular physiology. 208:476-486.
Li, H.X., X.Y. Zhao, L. Wang, Y.S. Wang, B. Kan, J.R. Xu, J. Li, Y.J. Wen, X.C. Peng, X. Chen, F. Yan, B. Ye, X.B. Du, J.M. Zhao, T. Yi, X.C. Chen, X.X. Du, Y.Q. Wei, and X. Zhao. 2010. Antitumor effect of mSurvivinThr34-->Ala in murine colon carcinoma when administered intravenously. Medical oncology. 27:1156-1163.
Li, X., X. Dang, and X. Sun. 2012. Expression of survivin and VEGF-C in breast cancer tissue and its relation to lymphatic metastasis. European journal of gynaecological oncology. 33:178-182.
Liston, P., W.G. Fong, and R.G. Korneluk. 2003. The inhibitors of apoptosis: there is more to life than Bcl2. Oncogene. 22:8568-8580.
Liu, T., B. Brouha, and D. Grossman. 2004. Rapid induction of mitochondrial events and caspase-independent apoptosis in Survivin-targeted melanoma cells. Oncogene. 23:39-48.
Lobrich, M., and P.A. Jeggo. 2007. The impact of a negligent G2/M checkpoint on genomic instability and cancer induction. Nature reviews. Cancer. 7:861-869.
Lowry, O.H., N.J. Rosebrough, A.L. Farr, and R.J. Randall. 1951. Protein measurement with the Folin phenol reagent. The Journal of biological chemistry. 193:265-275.
Lu, C.D., D.C. Altieri, and N. Tanigawa. 1998. Expression of a novel antiapoptosis gene, survivin, correlated with tumor cell apoptosis and p53 accumulation in gastric carcinomas. Cancer research. 58:1808-1812.
Lu, J., M. Tan, W.C. Huang, P. Li, H. Guo, L.M. Tseng, X.H. Su, W.T. Yang, W. Treekitkarnmongkol, M. Andreeff, F. Symmans, and D. Yu. 2009. Mitotic deregulation by survivin in ErbB2-overexpressing breast cancer cells contributes to Taxol resistance. Clinical cancer research : an official journal of the American Association for Cancer Research. 15:1326-1334.
Lu, S., B. Zhang, and Z. Wang. 2005. Expression of survivin, cyclinD1, p21(WAF1), caspase-3 in cervical cancer and its relation with prognosis. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban. 25:78-81.
Ma, X., W. Zheng, D. Wei, Y. Ma, T. Wang, J. Wang, Q. Liu, and S. Yang. 2006b. High-level expression, purification and pro-apoptosis activity of HIV-TAT-survivin (T34A) mutant to cancer cells in vitro. Journal of biotechnology. 123:367-378.
Makrides, S.C. 1996. Strategies for achieving high-level expression of genes in Escherichia coli. Microbiological reviews. 60:512-538.
McKay, T.R., S. Bell, T. Tenev, V. Stoll, R. Lopes, N.R. Lemoine, and I.A. McNeish. 2003. Procaspase 3 expression in ovarian carcinoma cells increases survivin transcription which can be countered with a dominant-negative mutant, survivin T34A; a combination gene therapy strategy. Oncogene. 22:3539-3547.
Mesri, M., N.R. Wall, J. Li, R.W. Kim, and D.C. Altieri. 2001. Cancer gene therapy using a survivin mutant adenovirus. The Journal of clinical investigation. 108:981-990.
Miyachi, K., K. Sasaki, S. Onodera, T. Taguchi, M. Nagamachi, H. Kaneko, and M. Sunagawa. 2003. Correlation between survivin mRNA expression and lymph node metastasis in gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association. 6:217-224.
Mogk, A., M.P. Mayer, and E. Deuerling. 2002. Mechanisms of protein folding: molecular chaperones and their application in biotechnology. Chembiochem : a European journal of chemical biology. 3:807-814.
Muchmore, S.W., J. Chen, C. Jakob, D. Zakula, E.D. Matayoshi, W. Wu, H. Zhang, F. Li, S.C. Ng, and D.C. Altieri. 2000. Crystal structure and mutagenic analysis of the inhibitor-of-apoptosis protein survivin. Molecular cell. 6:173-182.
Nakahara, T., A. Kita, K. Yamanaka, M. Mori, N. Amino, M. Takeuchi, F. Tominaga, S. Hatakeyama, I. Kinoyama, A. Matsuhisa, M. Kudoh, and M. Sasamata. 2007. YM155, a novel small-molecule survivin suppressant, induces regression of established human hormone-refractory prostate tumor xenografts. Cancer research. 67:8014-8021.
Nakahara, T., A. Kita, K. Yamanaka, M. Mori, N. Amino, M. Takeuchi, F. Tominaga, I. Kinoyama, A. Matsuhisa, M. Kudou, and M. Sasamata. 2011a. Broad spectrum and potent antitumor activities of YM155, a novel small-molecule survivin suppressant, in a wide variety of human cancer cell lines and xenograft models. Cancer science. 102:614-621.
Nakahara, T., K. Yamanaka, S. Hatakeyama, A. Kita, M. Takeuchi, I. Kinoyama, A. Matsuhisa, K. Nakano, T. Shishido, H. Koutoku, and M. Sasamata. 2011b. YM155, a novel survivin suppressant, enhances taxane-induced apoptosis and tumor regression in a human Calu 6 lung cancer xenograft model. Anti-cancer drugs. 22:454-462.
Nakamura, N., T. Yamauchi, M. Hiramoto, M. Yuri, M. Naito, M. Takeuchi, K. Yamanaka, A. Kita, T. Nakahara, I. Kinoyama, A. Matsuhisa, N. Kaneko, H. Koutoku, M. Sasamata, H. Yokota, S. Kawabata, and K. Furuichi. 2012. Interleukin enhancer-binding factor 3/NF110 is a target of YM155, a suppressant of survivin. Molecular & cellular proteomics : MCP. 11:M111 013243.
Niu, T.K., Y. Cheng, X. Ren, and J.M. Yang. 2010. Interaction of Beclin 1 with survivin regulates sensitivity of human glioma cells to TRAIL-induced apoptosis. FEBS letters. 584:3519-3524.
O'Connor, D.S., D. Grossman, J. Plescia, F. Li, H. Zhang, A. Villa, S. Tognin, P.C. Marchisio, and D.C. Altieri. 2000. Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin. Proceedings of the National Academy of Sciences of the United States of America. 97:13103-13107.
Olie, R.A., A.P. Simoes-Wust, B. Baumann, S.H. Leech, D. Fabbro, R.A. Stahel, and U. Zangemeister-Wittke. 2000. A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy. Cancer research. 60:2805-2809.
Peng, X.C., L. Yang, L.P. Yang, Y.Q. Mao, H.S. Yang, J.Y. Liu, D.M. Zhang, L.J. Chen, and Y.Q. Wei. 2008. Efficient inhibition of murine breast cancer growth and metastasis by gene transferred mouse survivin Thr34-->Ala mutant. Journal of experimental & clinical cancer research : CR. 27:46.
Rabhi-Essafi, I., A. Sadok, N. Khalaf, and D.M. Fathallah. 2007. A strategy for high-level expression of soluble and functional human interferon alpha as a GST-fusion protein in E. coli. Protein engineering, design & selection : PEDS. 20:201-209
Reddy, G.P., C.Y. Tiarks, L. Pang, J. Wuu, C.C. Hsieh, and P.J. Quesenberry. 1997. Cell cycle analysis and synchronization of pluripotent hematopoietic progenitor stem cells. Blood. 90:2293-2299.
Reed, J.C. 2001. The Survivin saga goes in vivo. The Journal of clinical investigation. 108:965-969.
Rieder, C.L., A. Schultz, R. Cole, and G. Sluder. 1994. Anaphase onset in vertebrate somatic cells is controlled by a checkpoint that monitors sister kinetochore attachment to the spindle. The Journal of cell biology. 127:1301-1310.
Riedl, S.J., and Y. Shi. 2004. Molecular mechanisms of caspase regulation during apoptosis. Nature reviews. Molecular cell biology. 5:897-907.
Roca, H., Z. Varsos, and K.J. Pienta. 2008. CCL2 protects prostate cancer PC3 cells from autophagic death via phosphatidylinositol 3-kinase/AKT-dependent survivin up-regulation. The Journal of biological chemistry. 283:25057-25073.
Rodel, F., B. Frey, W. Leitmann, G. Capalbo, C. Weiss, and C. Rodel. 2008. Survivin antisense oligonucleotides effectively radiosensitize colorectal cancer cells in both tissue culture and murine xenograft models. International journal of radiation oncology, biology, physics. 71:247-255.
Rosa, J., P. Canovas, A. Islam, D.C. Altieri, and S.J. Doxsey. 2006. Survivin modulates microtubule dynamics and nucleation throughout the cell cycle. Molecular biology of the cell. 17:1483-1493.
Rucker-Martin, C., M. Henaff, S.N. Hatem, E. Delpy, and J.J. Mercadier. 1999. Early redistribution of plasma membrane phosphatidylserine during apoptosis of adult rat ventricular myocytes in vitro. Basic research in cardiology. 94:171-179.
Samuel, T., K. Okada, M. Hyer, K. Welsh, J.M. Zapata, and J.C. Reed. 2005. cIAP1 Localizes to the nuclear compartment and modulates the cell cycle. Cancer research. 65:210-218.
Satoh, T., I. Okamoto, M. Miyazaki, R. Morinaga, A. Tsuya, Y. Hasegawa, M. Terashima, S. Ueda, M. Fukuoka, Y. Ariyoshi, T. Saito, N. Masuda, H. Watanabe, T. Taguchi, T. Kakihara, Y. Aoyama, Y. Hashimoto, and K. Nakagawa. 2009. Phase I study of YM155, a novel survivin suppressant, in patients with advanced solid tumors. Clinical cancer research : an official journal of the American Association for Cancer Research. 15:3872-3880.
Shi, Y. 2002. Mechanisms of caspase activation and inhibition during apoptosis. Molecular cell. 9:459-470.
Shin, S., B.J. Sung, Y.S. Cho, H.J. Kim, N.C. Ha, J.I. Hwang, C.W. Chung, Y.K. Jung, and B.H. Oh. 2001. An anti-apoptotic protein human survivin is a direct inhibitor of caspase-3 and -7. Biochemistry. 40:1117-1123.
Skoufias, D.A., C. Mollinari, F.B. Lacroix, and R.L. Margolis. 2000. Human survivin is a kinetochore-associated passenger protein. The Journal of cell biology. 151:1575-1582.
Song, Z., S. Liu, H. He, N. Hoti, Y. Wang, S. Feng, and M. Wu. 2004. A single amino acid change (Asp 53 --> Ala53) converts Survivin from anti-apoptotic to pro-apoptotic. Molecular biology of the cell. 15:1287-1296.
Song, Z., X. Yao, and M. Wu. 2003. Direct interaction between survivin and Smac/DIABLO is essential for the anti-apoptotic activity of survivin during taxol-induced apoptosis. The Journal of biological chemistry. 278:23130-23140.
Sun, C., D. Nettesheim, Z. Liu, and E.T. Olejniczak. 2005. Solution structure of human survivin and its binding interface with Smac/Diablo. Biochemistry. 44:11-17.
Suzuki, Y., Y. Nakabayashi, K. Nakata, J.C. Reed, and R. Takahashi. 2001. X-linked inhibitor of apoptosis protein (XIAP) inhibits caspase-3 and -7 in distinct modes. The Journal of biological chemistry. 276:27058-27063.
Takahashi, R., Q. Deveraux, I. Tamm, K. Welsh, N. Assa-Munt, G.S. Salvesen, and J.C. Reed. 1998. A single BIR domain of XIAP sufficient for inhibiting caspases. The Journal of biological chemistry. 273:7787-7790.
Takeuchi, H., J. Kim, A. Fujimoto, N. Umetani, T. Mori, A. Bilchik, R. Turner, A. Tran, C. Kuo, and D.S. Hoon. 2005. X-Linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling. Clinical cancer research : an official journal of the American Association for Cancer Research. 11:7621-7628.
Talbot, D.C., M. Ranson, J. Davies, M. Lahn, S. Callies, V. Andre, S. Kadam, M. Burgess, C. Slapak, A.L. Olsen, P.J. McHugh, J.S. de Bono, J. Matthews, A. Saleem, and P. Price. 2010. Tumor survivin is downregulated by the antisense oligonucleotide LY2181308: a proof-of-concept, first-in-human dose study. Clinical cancer research : an official journal of the American Association for Cancer Research. 16:6150-6158.
Tanioka, M., H. Nokihara, N. Yamamoto, Y. Yamada, K. Yamada, Y. Goto, T. Fujimoto, R. Sekiguchi, K. Uenaka, S. Callies, and T. Tamura. 2011. Phase I study of LY2181308, an antisense oligonucleotide against survivin, in patients with advanced solid tumors. Cancer chemotherapy and pharmacology. 68:505-511.
Tao, H., W. Liu, B.N. Simmons, H.K. Harris, T.C. Cox, and M.A. Massiah. 2010. Purifying natively folded proteins from inclusion bodies using sarkosyl, Triton X-100, and CHAPS. BioTechniques. 48:61-64.
Tenev, T., A. Zachariou, R. Wilson, M. Ditzel, and P. Meier. 2005. IAPs are functionally non-equivalent and regulate effector caspases through distinct mechanisms. Nature cell biology. 7:70-77.
Tran, J., Z. Master, J.L. Yu, J. Rak, D.J. Dumont, and R.S. Kerbel. 2002. A role for survivin in chemoresistance of endothelial cells mediated by VEGF. Proceedings of the National Academy of Sciences of the United States of America. 99:4349-4354.
Tsung, A., T. Kaizu, A. Nakao, L. Shao, B. Bucher, M.P. Fink, N. Murase, and D.A. Geller. 2005. Ethyl pyruvate ameliorates liver ischemia-reperfusion injury by decreasing hepatic necrosis and apoptosis. Transplantation. 79:196-204.
Tuncel, H., F. Shimamoto, H. Kaneko Guangying Qi, E. Aoki, H. Jikihara, S. Nakai, T. Takata, and M. Tatsuka. 2012. Nuclear Aurora B and cytoplasmic Survivin expression is involved in lymph node metastasis of colorectal cancer. Oncology letters. 3:1109-1114.
Tvegard, T., H. Soltani, H.C. Skjolberg, M. Krohn, E.A. Nilssen, S.E. Kearsey, B. Grallert, and E. Boye. 2007. A novel checkpoint mechanism regulating the G1/S transition. Genes & development. 21:649-654.
Uren, A.G., L. Wong, M. Pakusch, K.J. Fowler, F.J. Burrows, D.L. Vaux, and K.H. Choo. 2000. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Current biology : CB. 10:1319-1328.
van der Meijden, C.M., D.S. Lapointe, M.X. Luong, D. Peric-Hupkes, B. Cho, J.L. Stein, A.J. van Wijnen, and G.S. Stein. 2002. Gene profiling of cell cycle progression through S-phase reveals sequential expression of genes required for DNA replication and nucleosome assembly. Cancer research. 62:3233-3243.
Verdecia, M.A., H. Huang, E. Dutil, D.A. Kaiser, T. Hunter, and J.P. Noel. 2000. Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement. Nature structural biology. 7:602-608.
Voss, O.H., S. Batra, S.J. Kolattukudy, M.E. Gonzalez-Mejia, J.B. Smith, and A.I. Doseff. 2007. Binding of caspase-3 prodomain to heat shock protein 27 regulates monocyte apoptosis by inhibiting caspase-3 proteolytic activation. The Journal of biological chemistry. 282:25088-25099.
Walker, P.R., J. LeBlanc, and M. Sikorska. 1997. Evidence that DNA fragmentation in apoptosis is initiated and propagated by single-strand breaks. Cell death and differentiation. 4:506-515.
Wall, N.R., D.S. O'Connor, J. Plescia, Y. Pommier, and D.C. Altieri. 2003. Suppression of survivin phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis. Cancer research. 63:230-235.
Wang, F., J. Dai, J.R. Daum, E. Niedzialkowska, B. Banerjee, P.T. Stukenberg, G.J. Gorbsky, and J.M. Higgins. 2010. Histone H3 Thr-3 phosphorylation by Haspin positions Aurora B at centromeres in mitosis. Science. 330:231-235.
Wang, J., and Z. Wang. 2008. Negative regulation of caspase 3-cleaved PAK2 activity by protein phosphatase 1. Science in China. Series C, Life sciences / Chinese Academy of Sciences. 51:1-11.
Wang, Q., Z. Chen, X. Diao, and S. Huang. 2011. Induction of autophagy-dependent apoptosis by the survivin suppressant YM155 in prostate cancer cells. Cancer letters. 302:29-36.
Wang, W., H. Luo, and A. Wang. 2006. Expression of survivin and correlation with PCNA in osteosarcoma. Journal of surgical oncology. 93:578-584.
Wang, Z., S. Fukuda, and L.M. Pelus. 2004. Survivin regulates the p53 tumor suppressor gene family. Oncogene. 23:8146-8153.
Weickert, M.J., D.H. Doherty, E.A. Best, and P.O. Olins. 1996. Optimization of heterologous protein production in Escherichia coli. Current opinion in biotechnology. 7:494-499.
Wells, W.A., and A.W. Murray. 1996. Aberrantly segregating centromeres activate the spindle assembly checkpoint in budding yeast. The Journal of cell biology. 133:75-84.
Wender, P.A., D.J. Mitchell, K. Pattabiraman, E.T. Pelkey, L. Steinman, and J.B. Rothbard. 2000. The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: peptoid molecular transporters. Proceedings of the National Academy of Sciences of the United States of America. 97:13003-13008.
Weng, Y., B. Fei, A.L. Chi, and M. Cai. 2013. Inhibition of gastric cancer cell growth in vivo by overexpression of adeno-associated virus-mediated survivin mutant C84A. Oncology research. 20:411-417.
Wheatley, S.P., A. Carvalho, P. Vagnarelli, and W.C. Earnshaw. 2001. INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis. Current biology : CB. 11:886-890.
Wu, F., S. Buckley, K.C. Bui, A. Yee, H.Y. Wu, J. Liu, and D. Warburton. 1996. Cell cycle arrest in G0/G1 phase by contact inhibition and TGF-beta 1 in mink Mv1Lu lung epithelial cells. The American journal of physiology. 270:L879-888.
Xu, X., F. Hamhouyia, S.D. Thomas, T.J. Burke, A.C. Girvan, W.G. McGregor, J.O. Trent, D.M. Miller, and P.J. Bates. 2001. Inhibition of DNA replication and induction of S phase cell cycle arrest by G-rich oligonucleotides. The Journal of biological chemistry. 276:43221-43230.
Yamauchi, T., N. Nakamura, M. Hiramoto, M. Yuri, H. Yokota, M. Naitou, M. Takeuchi, K. Yamanaka, A. Kita, T. Nakahara, I. Kinoyama, A. Matsuhisa, N. Kaneko, H. Koutoku, M. Sasamata, M. Kobori, M. Katou, S. Tawara, S. Kawabata, and K. Furuichi. 2012. Sepantronium bromide (YM155) induces disruption of the ILF3/p54(nrb) complex, which is required for survivin expression. Biochemical and biophysical research communications. 425:711-716.
Yan, H., J. Thomas, T. Liu, D. Raj, N. London, T. Tandeski, S.A. Leachman, R.M. Lee, and D. Grossman. 2006. Induction of melanoma cell apoptosis and inhibition of tumor growth using a cell-permeable Survivin antagonist. Oncogene. 25:6968-6974.
Yu, D.D., C.T. Wang, H.S. Shi, Z.Y. Li, L. Pan, Q.Z. Yuan, F. Leng, Y. Wen, X. Chen, and Y.Q. Wei. 2010. Enhancement of cisplatin sensitivity in Lewis Lung carcinoma by liposome-mediated delivery of a survivin mutant. Journal of experimental & clinical cancer research : CR. 29:46.
Yuan, L., W.M. Yu, and C.K. Qu. 2003. DNA damage-induced G2/M checkpoint in SV40 large T antigen-immortalized embryonic fibroblast cells requires SHP-2 tyrosine phosphatase. The Journal of biological chemistry. 278:42812-42820.
Zhang, M., D.E. Latham, M.A. Delaney, and A. Chakravarti. 2005. Survivin mediates resistance to antiandrogen therapy in prostate cancer. Oncogene. 24:2474-2482.
Zhang, M.C., C.P. Hu, and Q. Chen. 2006. [Effect of down-regulation of survivin gene on apoptosis and cisplatin resistance in cisplatin resistant human lung adenocarcinoma A549/CDDP cells]. Zhonghua zhong liu za zhi [Chinese journal of oncology]. 28:408-412.
Zhang, R., T. Wang, K.N. Li, W.W. Qin, R. Chen, K. Wang, L.T. Jia, J. Zhao, W.H. Wen, Y.L. Meng, L.B. Yao, and A.G. Yang. 2008. A survivin double point mutant has potent inhibitory effect on the growth of hepatocellular cancer cells. Cancer biology & therapy. 7:547-554.