The identification of proteins involved in the early phases of cell death h
as relied primarily on the modular organization of shared sequences and str
uctural motifs of previously identified proteins in the apoptotic machinery
. This property has facilitated the isolation of proteins that interact wit
h each other through structural domains using yeast two-hybrid cloning Like
wise, the conservation in primary sequence of the various shared domains ha
s promoted the use of polymerase chain reaction and database search strateg
ies to isolate additional family members. Here, we discuss the use of datab
ase search strategies in the isolation of novel death proteins, as well as
how similar strategies may be extended to discover additional, novel cell d
eath proteins. (C) 1999 Academic Press.