| Structural highlights
Function
[BIRC5_HUMAN] Multitasking protein that has dual roles in promoting cell proliferation and preventing apoptosis. Component of a chromosome passage protein complex (CPC) which is essential for chromosome alignment and segregation during mitosis and cytokinesis. Acts as an important regulator of the localization of this complex; directs CPC movement to different locations from the inner centromere during prometaphase to midbody during cytokinesis and participates in the organization of the center spindle by associating with polymerized microtubules. The complex with RAN plays a role in mitotic spindle formation by serving as a physical scaffold to help deliver the RAN effector molecule TPX2 to microtubules. May counteract a default induction of apoptosis in G2/M phase. The acetylated form represses STAT3 transactivation of target gene promoters. May play a role in neoplasia. Inhibitor of CASP3 and CASP7. Isoform 2 and isoform 3 do not appear to play vital roles in mitosis. Isoform 3 shows a marked reduction in its anti-apoptotic effects when compared with the displayed wild-type isoform.[1] [2] [3] [4] [5] [6] [7] [8]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Survivin is a 16.5 kDa protein that is expressed during the G2/M phase of the cell cycle and is hypothesized to inhibit a default apoptotic cascade initiated in mitosis. This inhibitory function is coupled to survivin's localization to the mitotic spindle. To begin to address the structural basis of survivin's function, we report the X-ray crystal structure of a recombinant form of full length survivin to 2.58 A resolution. Survivin consists of two defined domains including an N-terminal Zn2+-binding BIR domain linked to a 65 A amphipathic C-terminal alpha-helix. The crystal structure reveals an extensive dimerization interface along a hydrophobic surface on the BIR domain of each survivin monomer. A basic patch acting as a sulfate/phosphate-binding module, an acidic cluster projecting off the BIR domain, and a solvent-accessible hydrophobic surface residing on the C-terminal amphipathic helix, are suggestive of functional protein-protein interaction surfaces.
Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement.,Verdecia MA, Huang H, Dutil E, Kaiser DA, Hunter T, Noel JP Nat Struct Biol. 2000 Jul;7(7):602-8. PMID:10876248[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Mahotka C, Wenzel M, Springer E, Gabbert HE, Gerharz CD. Survivin-deltaEx3 and survivin-2B: two novel splice variants of the apoptosis inhibitor survivin with different antiapoptotic properties. Cancer Res. 1999 Dec 15;59(24):6097-102. PMID:10626797
- ↑ Li F, Ambrosini G, Chu EY, Plescia J, Tognin S, Marchisio PC, Altieri DC. Control of apoptosis and mitotic spindle checkpoint by survivin. Nature. 1998 Dec 10;396(6711):580-4. PMID:9859993 doi:10.1038/25141
- ↑ Marusawa H, Matsuzawa S, Welsh K, Zou H, Armstrong R, Tamm I, Reed JC. HBXIP functions as a cofactor of survivin in apoptosis suppression. EMBO J. 2003 Jun 2;22(11):2729-40. PMID:12773388 doi:10.1093/emboj/cdg263
- ↑ Vong QP, Cao K, Li HY, Iglesias PA, Zheng Y. Chromosome alignment and segregation regulated by ubiquitination of survivin. Science. 2005 Dec 2;310(5753):1499-504. PMID:16322459 doi:10.1126/science.1120160
- ↑ Noton EA, Colnaghi R, Tate S, Starck C, Carvalho A, Ko Ferrigno P, Wheatley SP. Molecular analysis of survivin isoforms: evidence that alternatively spliced variants do not play a role in mitosis. J Biol Chem. 2006 Jan 13;281(2):1286-95. Epub 2005 Nov 16. PMID:16291752 doi:M508773200
- ↑ Xia F, Canovas PM, Guadagno TM, Altieri DC. A survivin-ran complex regulates spindle formation in tumor cells. Mol Cell Biol. 2008 Sep;28(17):5299-311. Epub 2008 Jun 30. PMID:18591255 doi:10.1128/MCB.02039-07
- ↑ Wang H, Holloway MP, Ma L, Cooper ZA, Riolo M, Samkari A, Elenitoba-Johnson KS, Chin YE, Altura RA. Acetylation directs survivin nuclear localization to repress STAT3 oncogenic activity. J Biol Chem. 2010 Nov 12;285(46):36129-37. doi: 10.1074/jbc.M110.152777. Epub, 2010 Sep 8. PMID:20826784 doi:10.1074/jbc.M110.152777
- ↑ Pavlyukov MS, Antipova NV, Balashova MV, Vinogradova TV, Kopantzev EP, Shakhparonov MI. Survivin monomer plays an essential role in apoptosis regulation. J Biol Chem. 2011 Jul 1;286(26):23296-307. doi: 10.1074/jbc.M111.237586. Epub, 2011 May 2. PMID:21536684 doi:10.1074/jbc.M111.237586
- ↑ Verdecia MA, Huang H, Dutil E, Kaiser DA, Hunter T, Noel JP. Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement. Nat Struct Biol. 2000 Jul;7(7):602-8. PMID:10876248 doi:10.1038/76838
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