BIRC5

BIRC5 Background

Baculoviral IAP repeat-containing protein 5 (BIRC5), also known as survivin, is a protein in humans that is encoded by the BIRC5 gene. Survivin contains a coiled-coil (CC) domain that interacts with chromosomal passenger proteins (including INCENP and borealin) and maintains the residency in the nucleus ^[1][2][3], and only one BIR domain that makes this protein unique compared to the other IAP family members ^[4][5]. The survivin protein is highly expressed in most human tumors and embryonic tissues but is barely detected in terminally differentiated cells ^[6][7]. Tamm I. et al. have shown that survivin inhibits both Bax and Fas-induced apoptotic pathways ^[8]. Survivin also plays a role in regulating cell mitosis ^[9]. The upregulation of survivin causes the functional loss of wild type p53. Tumors with high expression of survivin generally bear a poor prognosis and are associated with resistance to therapy. The expression of survivin is differential between cancer and normal tissues, making this protein a useful tool in cancer diagnosis and a promising therapeutic target ^[6][10]. A growing body of literature suggests the nuclear expression of survivin as a good prognostic marker. Disruption of the survivin induction pathway has increased apoptosis and inhibited tumor growth.

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[2] Engelsma D, Rodriguez JA, et al. Homodimerization antagonizes nuclear export of survivin [J]. Traffic, 2007, 8: 1495-1502.
[3] Jeyaprakash AA, Klein UR, et al. Structure of a Survivin-Borealin-INCENP core complex reveals how chromosomal passengers travel together [J]. Cell,2007, 131: 271-285.
[4] Verdecia MA, Huang H, et al. Structure of the human anti-apoptotic protein surviving reveals a dimeric arrangement [J]. Nat. Struct. Biol. 2000, 7 (7): 602-8.
[5] Chantalat L, Skoufias DA, et al. Crystal structure of human survivin reveals a bow tie-shaped dimer with two unusual alpha-helical extensions [J]. Mol. Cell.2000, 6 (1): 183-9.
[6] Sah NK, Khan Z, et al. Structural, functional and therapeutic biology of survivin [J]. Cancer Lett.2006, 244 (2): 164-71.
[7] Ambrosini G, Adida C, et al. A novel anti-apoptosis gene, survivin, expressed in cancer and lymphoma [J]. Nat Med,1997, 3: 917-921.
[8] Tamm I, Wang Y, et al. IAP-family protein survivin inhibits caspase activity and apoptosis induced by Fas (CD95), Bax, caspases, and anticancer drugs [J]. Cancer Res.1998, 58 (23): 5315-20.
[9] Ruchaud S, Carmena M, et al. Chromosomal passengers: conducting cell division [J]. Nat Rev Mol Cell Biol, 2007, 8: 798-812.
[10] Pennati M, Folini M, et al. Targeting survivin in cancer therapy [J]. Expert Opin. Ther. Targets.2008, 12 (4): 463-76.