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 repair system. Moreover, through reduction of cysteine residues, Ref-1 controls the activity of several transcription factors. It has been previously demonstrated that TSH up-regulates Ref-1 gene expression in thyroid cells. By using the rat FRTL-5 cell line, we demonstrate that TSH controls Ref-1 intracellular localization. Western blot experiments indicate that addition of TSH to the culture medium increases the Ref-1 cytoplasm-to-nucleus translocation. This phenomenon occurs at early times of TSH stimulation and is not dependent on protein neosynthesis. The Ref-1 cellular compartmentalization was also investigated in human thyroid tumors. A Ref-1 nuclear/cytoplasmic ratio difference between normal and cancerous thyroid tissues was observed. These results suggest that Ref-1 localization may have a critical role in the control of thyroid cell functions.
Tell
G
G
Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, Udine, Italy.
Pellizzari
L
L
Pucillo
C
C
Puglisi
F
F
Cesselli
D
D
Kelley
M R
MR
Di Loreto
C
C
Damante
G
G
D000818:Animals; D001692:Biological Transport; D019757:Carbon-Oxygen Lyases / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D006801:Humans; D051381:Rats; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013972:Thyrotropin / Q000502:physiology*
D013972:Thyrotropin; D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase