| Fas-Associated Death Domain (FADD) is a multi-functional adaptor molecule, best known for its role in transducing apoptotic signals from the Death Receptors, a subset of the Tumor Necrosis Factor Receptor (TNFR) superfamily. More recently, FADD has been implicated in numerous other contexts within the immune system, particularly in the proliferation of lymphocytes. The exact mechanism of FADD's role in T cell proliferation has been largely undefined. Using two mouse models of FADD, I have defined a dual role for FADD in proliferation of T cells during an immune response. While FADD maintains a lesser role in regulation of early cell cycle transitions, its dominant role during T cell expansion is as an inhibitor of necroptosis, a genetically programmed form of necrosis. FADD is able to compartmentalize its multiple cellular roles through phosphorylation and subcellular localization, ultimately lending to the intricate balance that is immune system homeostasis. |
