Mj. Kallio et al., Human inhibitor of apoptosis protein (IAP) survivin participates in regulation of chromosome segregation and mitotic exit, FASEB J, 15(12), 2001, pp. NIL_81-NIL_99
A signaling cascade termed the "spindle checkpoint" monitors interactions b
etween the kinetochores of chromosomes and spindle microtubules to prevent
precocious separation of sister chromatids. We have investigated the role o
f human inhibitor of apoptosis protein (IAP) survivin in regulation of cell
division. We demonstrate that HeLa and PtK1 cells transfected or microinje
cted with survivin anti-sense oligonucleotides produce significantly more p
olyploid and micronucleated progeny cells and show abortive mitosis when tr
eated with spindle poisons. Furthermore, perturbation of survivin function
in HeLa and PtK1 cells with anti-survivin antibodies at the beginning of mi
tosis affects the normal timing of separation of sister chromatids and dist
urbs the 3F3/2 phosphoepitope-recognized tension sensing mechanism of the s
pindle checkpoint. This leads to premature separation of sister chromatids,
which results in an uneven distribution of chromosomes between the newly f
ormed progeny cells-an event associated with tumor formation in many cell t
ypes. Finally, cells injected with anti-survivin antibody exit mitotic bloc
k induced with microtubule drugs. Our data suggest that survivin protein ma
y function within the spindle checkpoint pathway.