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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. NCBI Reference Sequence: NG_029069.1
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. 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. These data suggest survivin might provide a new target for cancer therapy that would discriminate between transformed and normal cells. Survivin expression is also highly regulated by the cell cycle and is only expressed in the G2-M phase. It is known that survivin localizes to the mitotic spindle by interaction with tubulin during mitosis and may play a contributing role in regulating mitosis. The molecular mechanisms of survivin regulation are still not well understood, but regulation of survivin seems to be linked to the p53 protein. It also is a direct target gene of the Wnt pathway and is upregulated by beta-catenin.
== IAP family of anti-apoptotic proteins ==
Survivin is a member of the IAP family of antiapoptotic proteins. It is shown to be conserved in function across evolution as homologues of the protein are found both in vertebrates and invertebrates. The first members of the IAPs identified were from the baculovirus IAPs, Cp-IAP and Op-IAP, which bind to and inhibit caspases as a mechanism that contributes to its efficient infection and replication cycle in the host.〔 Later, five more human IAPs that included XIAP, c-IAPl, C-IAP2, NAIP, and survivin were discovered. Survivin, like the others, was discovered by its structural homology to IAP family of proteins in human B-cell lymphoma. The human IAPs, XIAP, c-IAPl, C-IAP2 have been shown to bind to caspase-3 and -7, which are the effector caspases in the signaling pathway of apoptosis.〔 It is not known with absolute certainty though, how the IAPs inhibit apoptosis mechanistically at the molecular level.
A common feature that is present in all IAPs in the presence of a BIR (Baculovirus IAP Repeat, a ~70 amino acid motif) in one to three copies. It was shown by Tamm ''et al.'' that knocking out BIR2 from XIAP was enough to cause a loss of function in terms of XIAPs ability to inhibit caspases. This gives the implication that it is within these BIR motifs that contains the anti-apoptotic function of these IAPs. Survivin's one BIR domain shows a similar sequence compared to that of XIAP's BIR domains.〔
抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』
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