  FADD (Fas-associated death domain) is the main death receptor adaptor
molecule that transmits apoptotic signal. Recently, FADD protein was shown to
be expressed both in the cytoplasm and nucleus of in vitro cell lines. In
contrast to the cytoplasmic FADD, the nuclear FADD was shown to protect cells
from apoptosis. However, in vivo subcellular localization of FADD was still
unknown. Here, we demonstrated that FADD protein was expressed in both
cytoplasmic and nuclear compartment in ex vivo thyroid cells demonstrating that
nuclear sublocalization of FADD protein was a relevant phenomenon occurring in
vivo. Moreover, we showed that in the nucleus of untransformed thyroid cells
FADD localized mainly on euchromatin. We confirmed the nuclear localization of
FADD in ex vivo liver and showed that in this organ FADD and MBD4 interact
together. These results demonstrate that FADD is physiologically expressed in
the nucleus of cells in at least two mouse organs. This particular localization
opens new possible role of FADD in vivo either asan inhibitor of cell death, or
as a transcription factor, or as a molecular link between apoptosis and genome
surveillance.
