Survivin (BIRC5 or IAP4) is the smallest member of the inhibitor of apoptosis (IAP) proteins, containing only a single baculovirus IAP repeat (BIR) domain and lacking the C-terminal RING domain. Survivin has a theoretical molecular weight of 16.5 kDa (wild-type protein) and exists as ten splice variant forms including the most predominant isoforms, survivin-2B and surviving-DeltaEx3 (1). It also undergoes phosphorylation by PKA, Plk1, Cdk1, CKII and Aurora B at multiple sites (e.g. Serine 20 and Threonine 34, 53 and 117).
Besides being highly abundant in fetal development and expressed in proliferating adult cells such as activated T lymphocytes, erythroblasts, and self-renewing stem cells, survivin is generally absent in adult tissues. However, it is elevated in common cancers such as lung, colon, pancreas, breast and prostate where it drives proliferation, metastasis, poor prognosis, and decreased patient survival (2).
Survivin has been shown to be involved in multiple cellular processes including cell cycle progression, mitotic spindle assembly, kinetochore attachment, angiogenesis, migration, and its anti-apoptotic activity has been linked to both its monomeric and homodimeric forms. Survivin impacts the function of other IAP members, c-IAP1 and c-IAP-2, or modulates the inhibitory activity of XIAP against caspases by forming a stable complex with XIAP and HBXIP. During the intrinsic apoptotic pathway, survivin may prevent the release of mitochondrial APAF1 into the cytoplasm or hinder the association of SMAC with other IAPS, which results in prolonged cell survival (3).
1. Sah NK, Seniya C. (2015) Survivin splice variants and their diagnostic significance. Tumour Biol. 36(9):6623-31. PMID: 26245993
2. Lladser A, Sanhueza C, Kiessling R, Quest AF. (2011) Is survivin the potential Achilles' heel of cancer? Adv Cancer Res. 111:1-37. PMID: 21704829
3. Wheatley SP, Altieri DC. (2019) Survivin at a glance. J Cell Sci. 132(7). PMID: 30948431