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Survivin
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<h2 id="structure">Structure</h2> <p>Survivin is distinguished from other IAP family members in that it has only one <a href="/facts/Baculoviral_IAP_repeat/02s2PQFg">baculoviral IAP repeat</a> (BIR) domain. The protein is 16.5 kDa large and is the smallest member of the IAP family.<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> </p> <h2 id="function">Function</h2> <p>Survivin is expressed in a cell cycle-dependent manner, with highest levels in the G2/M phase. It localizes to the mitotic spindle during cell division and interacts with tubulin.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a><a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> Survivin plays important roles in regulating mitosis, inhibiting apoptosis, and promoting angiogenesis.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a><a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a> </p> <h2 id="role-in-cancer">Role in cancer</h2> <p>Survivin is highly expressed in most human cancers but is rarely detectable in normal adult tissues.<a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> Its overexpression in tumors correlates with increased drug resistance, reduced apoptosis, and poor patient prognosis. The aberrant regulation of survivin in cancer cells makes it an attractive target for cancer therapy.<a class="footnote-ref" id="fnref:10" href="#fn:10"><sup>10</sup></a> </p><p>Several approaches targeting survivin are being investigated as potential cancer treatments, including: </p> <ul><li>Antisense oligonucleotides to inhibit survivin expression</li> <li>Small molecule inhibitors of survivin function</li> <li>Immunotherapy approaches using survivin as a tumor-associated antigen</li> <li>Combination therapies to sensitize cancer cells to apoptosis by inhibiting survivin</li></ul> <h2 id="interactions">Interactions</h2> <p>Survivin has been shown to interact with: </p> <ul><li><a href="/facts/Aurora_B_kinase/4CW3Xqq7">Aurora B kinase</a><a class="footnote-ref" id="fnref:11" href="#fn:11"><sup>11</sup></a></li> <li><a href="/facts/CDCA8/fQt4nD7G">CDCA8</a><a class="footnote-ref" id="fnref:12" href="#fn:12"><sup>12</sup></a></li> <li><a href="/facts/Caspase_3/FpjEwtwR">Caspase 3</a><a class="footnote-ref" id="fnref:13" href="#fn:13"><sup>13</sup></a></li> <li><a href="/facts/Caspase_7/gIhEAr4q">Caspase 7</a><a class="footnote-ref" id="fnref:14" href="#fn:14"><sup>14</sup></a></li> <li><a href="/facts/Diablo_homolog/hloWlDmQ">DIABLO</a><a class="footnote-ref" id="fnref:15" href="#fn:15"><sup>15</sup></a></li> <li><a href="/facts/INCENP/f79ayYcw">INCENP</a><a class="footnote-ref" id="fnref:16" href="#fn:16"><sup>16</sup></a></li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>"Gene: BIRC5, baculoviral IAP repeat containing 5". NCBI. Retrieved 2024-02-06. <a href="https://www.ncbi.nlm.nih.gov/gene/332" target="_blank">https://www.ncbi.nlm.nih.gov/gene/332</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, et al. (December 1998). "IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs". Cancer Research. 58 (23): 5315–5320. PMID 9850056. <a href="/wiki/PMID_(identifier)" target="_blank">/wiki/PMID_(identifier)</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>Ambrosini G, Adida C, Altieri DC (August 1997). "A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma". Nature Medicine. 3 (8): 917–921. doi:10.1038/nm0897-917. PMID 9256286. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Chantalat L, Skoufias DA, Kleman JP, Jung B, Dideberg O, Margolis RL (July 2000). "Crystal structure of human survivin reveals a bow tie-shaped dimer with two unusual alpha-helical extensions". Molecular Cell. 6 (1): 183–189. doi:10.1016/s1097-2765(05)00020-1. PMID 10949039. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, et al. (December 1998). "Control of apoptosis and mitotic spindle checkpoint by survivin". Nature. 396 (6711): 580–584. Bibcode:1998Natur.396..580L. doi:10.1038/25141. PMID 9859993. <a href="/wiki/Bibcode_(identifier)" target="_blank">/wiki/Bibcode_(identifier)</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>Mita AC, Mita MM, Nawrocki ST, Giles FJ (August 2008). "Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics". Clinical Cancer Research. 14 (16): 5000–5005. doi:10.1158/1078-0432.CCR-08-0746. PMID 18698017. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Mita AC, Mita MM, Nawrocki ST, Giles FJ (August 2008). "Survivin: key regulator of mitosis and apoptosis and novel target for cancer therapeutics". Clinical Cancer Research. 14 (16): 5000–5005. doi:10.1158/1078-0432.CCR-08-0746. PMID 18698017. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Giodini A, Kallio MJ, Wall NR, Gorbsky GJ, Tognin S, Marchisio PC, et al. (May 2002). "Regulation of microtubule stability and mitotic progression by survivin". Cancer Research. 62 (9): 2462–2467. PMID 11980633. <a href="/wiki/PMID_(identifier)" target="_blank">/wiki/PMID_(identifier)</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>Ambrosini G, Adida C, Altieri DC (August 1997). "A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma". Nature Medicine. 3 (8): 917–921. doi:10.1038/nm0897-917. PMID 9256286. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> <li id="fn:10"><p>Altieri DC (November 2003). "Survivin, versatile modulation of cell division and apoptosis in cancer". Oncogene. 22 (53): 8581–8589. doi:10.1038/sj.onc.1207113. PMID 14634620. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:10" class="footnote-back-ref">↩</a></p></li> <li id="fn:11"><p>Chen J, Jin S, Tahir SK, Zhang H, Liu X, Sarthy AV, et al. (January 2003). "Survivin enhances Aurora-B kinase activity and localizes Aurora-B in human cells". The Journal of Biological Chemistry. 278 (1): 486–490. doi:10.1074/jbc.M211119200. PMID 12419797. <a href="https://doi.org/10.1074%2Fjbc.M211119200" target="_blank">https://doi.org/10.1074%2Fjbc.M211119200</a> <a href="#fnref:11" class="footnote-back-ref">↩</a></p></li> <li id="fn:12"><p>Gassmann R, Carvalho A, Henzing AJ, Ruchaud S, Hudson DF, Honda R, et al. (July 2004). "Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle". The Journal of Cell Biology. 166 (2): 179–191. doi:10.1083/jcb.200404001. PMC 2172304. PMID 15249581. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172304" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172304</a> <a href="#fnref:12" class="footnote-back-ref">↩</a></p></li> <li id="fn:13"><p>Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, et al. (December 1998). "IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs". Cancer Research. 58 (23): 5315–5320. PMID 9850056. <a href="/wiki/PMID_(identifier)" target="_blank">/wiki/PMID_(identifier)</a> <a href="#fnref:13" class="footnote-back-ref">↩</a></p></li> <li id="fn:14"><p>Tamm I, Wang Y, Sausville E, Scudiero DA, Vigna N, Oltersdorf T, et al. (December 1998). "IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs". Cancer Research. 58 (23): 5315–5320. PMID 9850056. <a href="/wiki/PMID_(identifier)" target="_blank">/wiki/PMID_(identifier)</a> <a href="#fnref:14" class="footnote-back-ref">↩</a></p></li> <li id="fn:15"><p>Song Z, Yao X, Wu M (June 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 (25): 23130–23140. doi:10.1074/jbc.M300957200. PMID 12660240. <a href="https://doi.org/10.1074%2Fjbc.M300957200" target="_blank">https://doi.org/10.1074%2Fjbc.M300957200</a> <a href="#fnref:15" class="footnote-back-ref">↩</a></p></li> <li id="fn:16"><p>Wheatley SP, Carvalho A, Vagnarelli P, Earnshaw WC (June 2001). "INCENP is required for proper targeting of Survivin to the centromeres and the anaphase spindle during mitosis". Current Biology. 11 (11): 886–890. Bibcode:2001CBio...11..886W. doi:10.1016/s0960-9822(01)00238-x. PMID 11516652. <a href="/wiki/Bibcode_(identifier)" target="_blank">/wiki/Bibcode_(identifier)</a> <a href="#fnref:16" class="footnote-back-ref">↩</a></p></li> </ol>