The death effector domain protein family: regulators of cellular homeostasis

The death effector domain (DED) occurs in proteins that regulate programmed cell death. Both pro- and anti-apoptotic proteins containing DEDs have been identified. For Fas and possibly other death receptors, homotypic DIED interactions connect the Fas-associated death domain (FADD) protein to caspase-8 and caspase-10 to mediate formation of the death-inducing signal complex. This complex can be inhibited by other DED-containing proteins. Accumulating evidence now suggests that DED-containing proteins have additional roles in controlling pathways of cellular activation and proliferation. Thus, the DED defines a family of proteins that may be pivotal to cellular homeostasis by establishing a 'cell renewal set point' that coregulates proliferation and apoptosis in parallel.