Survivin

For the Bastille song, see Survivin'.

Survivin, also called baculoviral inhibitor of apoptosis repeat-containing 5 or BIRC5, is a protein that, in humans, is encoded by the BIRC5 gene.^[5]

BIRC5
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1E31, 1F3H, 1XOX, 2QFA, 2RAW, 2RAX, 3UEC, 3UED, 3UEE, 3UEF, 3UEG, 3UEH, 3UEI, 3UIG, 3UIH, 3UII, 3UIJ, 3UIK, 4A0I, 4A0J, 4A0N
Identifiers
Aliases	BIRC5, API4, EPR-1, baculoviral IAP repeat containing 5
External IDs	OMIM: 603352; MGI: 1203517; HomoloGene: 37450; GeneCards: BIRC5; OMA:BIRC5 - orthologs
Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q25.3 Start 78,214,186 bp[1] End 78,225,636 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 E2 Start 117,740,077 bp[2] End 117,746,569 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ventricular zone ganglionic eminence gonad left testis right testis mucosa of transverse colon bone marrow trabecular bone stromal cell of endometrium testicle Top expressed in fetal liver hematopoietic progenitor cell primary oocyte otic placode endocardial cushion zygote maxillary prominence mandibular prominence dermis abdominal wall blastocyst More reference expression data BioGPS More reference expression data
Gene ontology Molecular function peptidase inhibitor activity cobalt ion binding chaperone binding protein homodimerization activity metal ion binding ubiquitin-protein transferase activity tubulin binding cysteine-type endopeptidase inhibitor activity involved in apoptotic process protein binding identical protein binding protein heterodimerization activity enzyme binding microtubule binding zinc ion binding cysteine-type endopeptidase inhibitor activity Cellular component cytosol spindle chromosome nucleoplasm chromosome passenger complex nuclear chromosome interphase microtubule organizing center spindle microtubule centriole cytoplasmic microtubule cytoskeleton microtubule kinetochore midbody cytoplasm chromosome, centromeric region nucleus Biological process negative regulation of peptidase activity negative regulation of cysteine-type endopeptidase activity involved in apoptotic process regulation of transcription, DNA-templated inhibition of cysteine-type endopeptidase activity involved in apoptotic process establishment of chromosome localization chromosome segregation positive regulation of mitotic cell cycle positive regulation of exit from mitosis transcription, DNA-templated cell division protein phosphorylation mitotic spindle assembly regulation of signal transduction G2/M transition of mitotic cell cycle positive regulation of cell population proliferation protein-containing complex localization cell cycle negative regulation of transcription, DNA-templated apoptotic process regulation of apoptotic process negative regulation of apoptotic process regulation of mitotic cell cycle mitotic cell cycle hearing mitotic cytokinesis mitotic spindle assembly checkpoint signaling cytokine-mediated signaling pathway protein ubiquitination negative regulation of endopeptidase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 332 11799 Ensembl ENSG00000089685 ENSMUSG00000017716 UniProt O15392 O70201 RefSeq (mRNA) NM_001012270 NM_001012271 NM_001168 NM_001012272 NM_001012273 NM_009689 RefSeq (protein) NP_001012270 NP_001012271 NP_001159 NP_001012273 NP_033819 Location (UCSC) Chr 17: 78.21 – 78.23 Mb Chr 11: 117.74 – 117.75 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Survivin is a member of the inhibitor of apoptosis (IAP) family. The survivin protein functions to inhibit caspase activation, thereby leading to negative regulation of apoptosis or programmed cell death.^[6] This has been shown by disruption of survivin induction pathways leading to increase in apoptosis and decrease in tumour growth. The survivin protein is expressed highly in most human tumours and fetal tissue, but is completely absent in terminally differentiated cells.^[7]

Structure

Survivin is distinguished from other IAP family members in that it has only one baculoviral IAP repeat (BIR) domain. The protein is 16.5 kDa large and is the smallest member of the IAP family.^[8]

Function

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.^[9][10] Survivin plays important roles in regulating mitosis, inhibiting apoptosis, and promoting angiogenesis.^[10][11]

Role in cancer

Survivin is highly expressed in most human cancers but is rarely detectable in normal adult tissues.^[7] 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.^[12]

Several approaches targeting survivin are being investigated as potential cancer treatments, including:

• Antisense oligonucleotides to inhibit survivin expression
• Small molecule inhibitors of survivin function
• Immunotherapy approaches using survivin as a tumor-associated antigen
• Combination therapies to sensitize cancer cells to apoptosis by inhibiting survivin

Interactions

Survivin has been shown to interact with:

• Aurora B kinase^[13]
• CDCA8^[14]
• Caspase 3^[6]
• Caspase 7^[6]
• DIABLO^[15]
• INCENP^[16]

References

1. GRCh38: Ensembl release 89: ENSG00000089685 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000017716 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Gene: BIRC5, baculoviral IAP repeat containing 5". NCBI. Retrieved 2024-02-06.
6. 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.
7. 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.
8. 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.
9. 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. doi:10.1038/25141. PMID 9859993.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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. doi:10.1016/s0960-9822(01)00238-x. PMID 11516652.