1876-8946/09 2009 Bentham Open Open Access In Vivo Localization of Fas-Associated Death Domain Protein in the Nucleus and Cytoplasm of Normal Thyroid and Liver Cells

Abstract: FADD (Fas-associated death domain) is the main death receptor adaptor molecule that transmits apoptotic sig-nal. Recently, FADD protein was shown to be expressed both in the cytoplasm and nucleus of in vitro cell lines. In con-trast to the cytoplasmic FADD, the nuclear FADD was shown to protect cells from apoptosis. However, in vivo subcellu-lar localization of FADD was still unknown. Here, we demonstrated that FADD protein was expressed in both cytoplas-mic 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 nu-cleus of cells in at least two mouse organs. This particular localization opens new possible role of FADD in vivo either as an inhibitor of cell death, or as a transcription factor, or as a molecular link between apoptosis and genome surveillance