In response to DNA damage and genotoxic stress, the p53 tumor suppressor tr
iggers either cell cycle arrest or apoptosis. The G(2) arrest after damage
is, in part, mediated by the p53 target, 14-3-3 sigma (sigma). Colorectal t
umor cells lacking a are exquisitely sensitive to DNA damage. Here we analy
zed the mechanism of this sensitivity in sigma (-/-) as compared with sigma
(+/+) human colorectal tumor cells. Exposure to adriamycin resulted in rap
id apoptosis only in sigma (-/-) cells. This was further characterized by c
aspase-3 activation, p21(CIP1) cleavage, and CDK2 activation. Moreover, Bax
was rapidly translocated out of the cytoplasm, and cytochrome c was releas
ed in sigma (-/-) cells. Transient adenovirus-mediated reconstitution of or
in the sigma (-/-) cells led to effective rescue of this phenotype and pro
tected cells against apoptosis. The association of sigma, Bax, and CDK1 in
protein complexes may be the basis for this antiapoptotic mechanism. In con
clusion, a not only enforces the p53-dependent G(2) arrest but also delays
the apoptotic signal transduction.