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TSH controls Ref-1 nuclear translocation in thyroid cells.

G Tell1, L Pellizzari, C Pucillo

  • 1Dipartimento di Scienze e Tecnologie Biomediche, Università di Udine, Udine, Italy.

Journal of Molecular Endocrinology
|June 1, 2000
PubMed
Summary
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Thyroid-stimulating hormone (TSH) influences the location of Ref-1 protein within thyroid cells, moving it to the nucleus. This Ref-1 localization change in thyroid tumors suggests a role in cell function control.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Ref-1 (APE) is a bifunctional protein crucial for DNA repair and transcription factor regulation.
  • Thyroid-stimulating hormone (TSH) is known to increase Ref-1 gene expression in thyroid cells.

Purpose of the Study:

  • To investigate the effect of TSH on Ref-1 intracellular localization in thyroid cells.
  • To examine Ref-1 cellular compartmentalization in human thyroid tumors.

Main Methods:

  • Utilized the rat FRTL-5 cell line for TSH stimulation experiments.
  • Employed Western blot analysis to assess Ref-1 protein levels and translocation.
  • Compared Ref-1 nuclear/cytoplasmic ratios in normal versus cancerous thyroid tissues.

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Main Results:

  • TSH stimulation significantly increases Ref-1 translocation from the cytoplasm to the nucleus in FRTL-5 cells.
  • This cytoplasmic-to-nuclear shift occurs rapidly and is independent of new protein synthesis.
  • A distinct difference in the nuclear/cytoplasmic Ref-1 ratio was observed between normal and cancerous thyroid tissues.

Conclusions:

  • TSH actively regulates Ref-1 intracellular localization in thyroid cells.
  • Altered Ref-1 compartmentalization in thyroid tumors may be functionally significant.
  • Ref-1 localization plays a critical role in controlling thyroid cell functions.