The molecular basis of programmed cell death (PCD) is unknown. An impo
rtant clue is provided by the Bcl-2 protein, which can protect many ce
ll types from PCD, although it is not known where or how it acts. Nucl
ear condensation, DNA fragmentation and a requirement for new RNA and
protein synthesis are often considered hallmarks of PCD. We show here,
however, that anucleate cytoplasts can undergo PCD and that Bcl-2 and
extracellular survival signals can protect them, indicating that, in
some cases at least, the nucleus is not required for PCD or for Bcl-2
or survival factor protection. We propose that PCD, like the cell cycl
e, is orchestrated by a cytoplasmic regulator that has multiple intrac
ellular targets.