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FADD (Fas-associated death domain) is the main death receptor adaptormolecule that transmits apoptotic signal. Recently, FADD protein was shown tobe expressed both in the cytoplasm and nucleus of in vitro cell lines. Incontrast to the cytoplasmic FADD, the nuclear FADD was shown to protect cellsfrom apoptosis. However, in vivo subcellular localization of FADD was stillunknown. Here, we demonstrated that FADD protein was expressed in bothcytoplasmic and nuclear compartment in ex vivo thyroid cells demonstrating thatnuclear sublocalization of FADD protein was a relevant phenomenon occurring invivo. Moreover, we showed that in the nucleus of untransformed thyroid cellsFADD localized mainly on euchromatin. We confirmed the nuclear localization ofFADD in ex vivo liver and showed that in this organ FADD and MBD4 interacttogether. These results demonstrate that FADD is physiologically expressed inthe nucleus of cells in at least two mouse organs. This particular localizationopens new possible role of FADD in vivo either asan inhibitor of cell death, oras a transcription factor, or as a molecular link between apoptosis and genomesurveillance.

In Vivo Localization of Fas-Associated Death Domain Protein in the Nucleus and Cytoplasm of Normal Thyroid and Liver Cells