TSH controls Ref-1 nuclear translocation in thyroid cells

Ref-1 (called also APE) is a bifunctional protein playing a role in a large variety of cell functions, it is a major member of the DNA base excision r epair system. Moreover, through reduction of cysteine residues, Ref-1 contr ols the activity of several transcription factors. It has been previously d emonstrated that TSH up-regulates Ref-1 gene expression in thyroid cells. B y using the rat FRTL-5 cell line, we demonstrate that TSH controls Ref-1 in tracellular localization. Western blot experiments indicate that addition o f TSH to the culture medium increases the Ref-1 cytoplasm-to-nucleus transl ocation. This phenomenon occurs at early times of TSH stimulation and is no t dependent on protein neosynthesis. The Ref-1 cellular compartmentalizatio n was also investigated in human thyroid tumors. A Ref-1 nuclear/cytoplasmi c ratio difference between normal and cancerous thyroid tissues was observe d. These results suggest that Ref-1 localization may have a critical role i n the control of thyroid cell functions.