Cytoplasmic TSC-22 (transforming growth factor-beta-stimulated clone-22) markedly enhances the radiation sensitivity of salivary gland cancer cells.
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.
Hino
Satoshi
S
Second Department of Oral and Maxillofacial Surgery, Tokushima University School of Dentistry, 3-18-15 Kuramoto, Tokushima, 770-8504, Japan.
Kawamata
Hitoshi
H
Omotehara
Fumie
F
Uchida
Daisuke
D
Miwa
Yoshihiro
Y
Begum
Nasima-Mila
NM
Yoshida
Hideo
H
Sato
Mitsunobu
M
Fujimori
Takahiro
T
D021581:Active Transport, Cell Nucleus / Q000502:physiology / Q000528:radiation effects; D020816:Amino Acid Motifs / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D003593:Cytoplasm / Q000378:metabolism / Q000528:radiation effects; D049452:Green Fluorescent Proteins; D006801:Humans; D016350:Leucine Zippers / Q000502:physiology; D008164:Luminescent Proteins / Q000235:genetics; D019913:Nuclear Localization Signals / Q000502:physiology; D011836:Radiation Tolerance / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000494:pharmacology*; D012468:Salivary Gland Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D017384:Sequence Deletion; D014162:Transfection; D014407:Tumor Cells, Cultured
D008164:Luminescent Proteins; D019913:Nuclear Localization Signals; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C099726:TSC22D1 protein, human; D049452:Green Fluorescent Proteins