G1P3, an interferon inducible gene 6-16, is expressed in gastric cancers and inhibits mitochondrial-mediated apoptosis in gastric cancer cell line TMK-1 cell.
Expression of an interferon inducible gene 6-16, G1P3, increases not only in type I interferon-treated cells but also in human senescent fibroblasts. However, the function of 6-16 protein is unknown. Here we report that 6-16 is 34 kDa glycosylated protein and localized at mitochondria. Interestingly, 6-16 is expressed at high levels in gastric cancer cell lines and tissues. One of exceptional gastric cancer cell line, TMK-1, which do not express detectable 6-16, is sensitive to apoptosis induced by cycloheximide (CHX), 5-fluorouracil (5-FU) and serum-deprivation. Ectopic expression of 6-16 gene restored the induction of apoptosis and inhibited caspase-3 activity in TMK-1 cells. Thus 6-16 protein has anti-apoptotic function through inhibiting caspas-3. This anti-apoptotic function is expressed through inhibition of the depolarization of mitochondrial membrane potential and release of cytochrome c. By two-hybrid screening, we found that 6-16 protein interacts with calcium and integrin binding protein, CIB/KIP/Calmyrin (CIB), which interacts with presenilin 2, a protein involved in Alzheimer's disease. These protein interactions possibly play a pivotal role in the regulation of apoptosis, for which further detailed analyses are need. These results overall indicate that 6-16 protein may have function as a cell survival protein by inhibiting mitochondrial-mediated apoptosis.
Tahara
Eiji
E
Department of Cellular and Molecular Biology, Division of Integerated Medical Science, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minamiku-ku, Hiroshima 734-8551, Japan.
Tahara
Hidetoshi
H
Kanno
Masamoto
M
Naka
Kazuhito
K
Takeda
Yayoi
Y
Matsuzaki
Takeshi
T
Yamazaki
Ryuta
R
Ishihara
Hiroto
H
Yasui
Wataru
W
Barrett
J Carl
JC
Ide
Toshinori
T
Tahara
Eiichi
E
D017209:Apoptosis; D015152:Blotting, Northern; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000502:physiology; D024101:Mitochondrial Proteins; D011506:Proteins / Q000235:genetics* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured
C468762:IFI6 protein, human; D024101:Mitochondrial Proteins; D011506:Proteins