Cytoplasmic TSC-22 (transforming growth factor-beta-stimulated clone-22) markedly enhances the radiation sensitivity of salivary gland cancer cells

Biochem Biophys Res Commun. 2002 Apr 12;292(4):957-63. doi: 10.1006/bbrc.2002.6776.

Abstract

We transfected a salivary gland cancer cell line, TYS, with three different forms of TSC-22 (transforming growth factor-beta-stimulated clone-22) gene: full-length TSC-22 (TSC-22FL) containing nuclear export signal, TSC-box and leucine zipper, truncated TSC-22 (TSC-22LZ) containing only TSC-box and leucine zipper, and truncated TSC-22 with nuclear localization signal (NLS-TSC-22LZ). High expression of TSC-22FL in the cytoplasm markedly enhanced the radiation-sensitivity of TYS cells, while, moderate expression of TSC-22FL marginally affected the radiation-sensitivity. TSC-22LZ, which was expressed in the cytoplasm and the nucleus, enhanced the radiation-sensitivity of TYS cells irrespective to its expression level. NLS-TSC-22LZ, which was expressed only in the nucleus, marginally affected the radiation-sensitivity of the cells even at high expression level. Interestingly, cytoplasmic TSC-22 translocates to nucleus concomitant with radiation-induced apoptosis. These results suggest that cytoplasmic localization of TSC-22 and translocation of TSC-22 from cytoplasm to nucleus is important for regulating the cell death signal after irradiation-induced DNA damage.

MeSH terms

  • Active Transport, Cell Nucleus / physiology
  • Active Transport, Cell Nucleus / radiation effects
  • Amino Acid Motifs / physiology
  • Apoptosis / drug effects
  • Apoptosis / radiation effects
  • Cell Cycle / radiation effects
  • Cell Division / drug effects
  • Cell Division / radiation effects
  • Cell Nucleus / metabolism
  • Cell Nucleus / radiation effects
  • Cytoplasm / metabolism
  • Cytoplasm / radiation effects
  • Green Fluorescent Proteins
  • Humans
  • Leucine Zippers / physiology
  • Luminescent Proteins / genetics
  • Nuclear Localization Signals / physiology
  • Radiation Tolerance / drug effects*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / pharmacology*
  • Salivary Gland Neoplasms / drug therapy
  • Salivary Gland Neoplasms / metabolism*
  • Sequence Deletion
  • Transfection
  • Tumor Cells, Cultured

Substances

  • Luminescent Proteins
  • Nuclear Localization Signals
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • TSC22D1 protein, human
  • Green Fluorescent Proteins