Apoptosis: Searching for FLASH domains

During programmed cell death (apoptosis), a protein named FLASH is required to regulate the proteolytic cascade that ends in the death of the cell. Imai and co-workers have reported1 that FLASH appears to be a functional analogue of two other apoptotic proteins, mammalian Apaf-1 and its nematode homologue CED-4, and that FLASH contains an amino-acid sequence motif that is homologous to the ATPase domain of Apaf-1, to the CED-4 sequence, and to a family of plant stress-resistant proteins that are apoptotic ATPases2. Furthermore, FLASH contains two other domains (DRD) that are apparently related to the death-effector domain (DED)1, an adaptor sequence that mediates interactions between proteins of the apoptosis machinery2. These findings should help to explain the mechanism of action of this important protein. However, we have been unable to confirm the exist-ence of these domains after re-examining the FLASH sequence.