Inhibitors of programmed cell death (apoptosis) aberrantly prolonging
cell viability may contribute to cancer(1) by facilitating the insurge
nce of mutations and by promoting resistance to therapy(2). Despite th
e identification of several new apoptosis inhibitors related to bcl-2(
2,3) or to the baculovirus IAP gene(4-9), it is not clear whether apop
tosis inhibition plays a general role in neoplasia. Here, we describe
a new human gene encoding a structurally unique IAP apoptosis inhibito
r, designated survivin. Survivin contains a single baculovirus IAP rep
eat and lacks a carboxyl-terminal RING finger. Present during fetal de
velopment, survivin is undetectable in terminally differentiated adult
tissues. However, survivin becomes prominently expressed in transform
ed cell lines and in all the most common human cancers of lung, colon,
pancreas, prostate and breast, in vivo. Survivin is also found in app
roximately 50% of high-grade non-Hodgkin's lymphomas (centroblastic, i
mmunoblastic), but not in low-grade lymphomas (lymphocytic). Recombina
nt expression of survivin counteracts apoptosis of B lymphocyte precur
sors deprived of interleukin 3 (IL-3). These findings suggest that apo
ptosis inhibition may be a general feature of neoplasia and identify s
urvivin as a potential new target for apoptosis-based therapy in cance
r and lymphoma.