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

TL;DR

This study reveals that FADD protein is localized in both nucleus and cytoplasm in vivo within thyroid and liver cells, suggesting new roles in cell survival, transcription regulation, or genome surveillance.

Contribution

It demonstrates in vivo nuclear localization of FADD in thyroid and liver cells, expanding understanding of its cellular functions beyond apoptosis.

Findings

FADD is present in both nucleus and cytoplasm in vivo.

Nuclear FADD associates mainly with euchromatin.

FADD interacts with MBD4 in liver cells.

Abstract

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.