C. Brancolini et al., DISMANTLING CELL-CELL CONTACTS DURING APOPTOSIS IS COUPLED TO A CASPASE-DEPENDENT PROTEOLYTIC CLEAVAGE OF BETA-CATENIN, The Journal of cell biology, 139(3), 1997, pp. 759-771
Cell death by apoptosis is a tightly regulated process that requires c
oordinated modification in cellular architecture. The caspase protease
family has been shown to play a key role in apoptosis. Here we report
that specific and ordered changes in the actin cytoskeleton take plac
e during apoptosis. In this context, we have dissected one of the firs
t hallmarks in cell death, represented by the severing of contacts amo
ng neighboring cells. More specifically, we provide demonstration for
the mechanism that could contribute to the disassembly of cytoskeletal
organization at cell-cell adhesion. In fact, beta-catenin, a known re
gulator of cell-cell adhesion, is proteolytically processed in differe
nt cell types after induction of apoptosis. Caspase-3 (cpp32/apopain/y
ama) cleaves in vitro translated beta-catenin into a form which is sim
ilar in size to that observed in cells undergoing apoptosis. beta-Cate
nin cleavage, during apoptosis in vivo and after caspase-3 treatment i
n vitro, removes the amino- and carboxy-terminal regions of the protei
n. The resulting beta-catenin product is unable to bind alpha-catenin
that is responsible for actin filament binding and organization. This
evidence indicates that connection with actin filaments organized at c
ell-cell contacts could be dismantled during apoptosis. Our observatio
ns suggest that caspases orchestrate the specific and sequential chang
es in the actin cytoskeleton occurring during cell death via cleavage
of different regulators of the microfilament system.