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
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
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DOI：
10.1007/s00262-004-0645-2
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发表时间：
2005-08-01
影响因子：
5.8
通讯作者：
Tahara, E
中科院分区：
文献类型：
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作者：
Tahara, E;Tahara, H;Tahara, E
干扰素诱导基因6-16 G1P3的表达不仅在I型干扰素处理的细胞中增加，而且在人衰老的成纤维细胞中也增加。然而，6-16蛋白的功能尚不清楚。在此，我们报道了6-16是34 kDa的糖基化蛋白，定位于线粒体。有趣的是，6-16在胃癌细胞系和组织中高水平表达。TMK-1是一种特殊的胃癌细胞系，它不表达可检测到的6-16，对放线菌酮(CHX)、5-氟尿嘧啶(5-FU)和去血清诱导的细胞凋亡非常敏感。异位表达6-16基因可恢复TMK-1细胞的凋亡诱导作用，并抑制caspase-3活性。因此，6-16蛋白通过抑制caspas-3发挥抗凋亡作用。通过抑制线粒体膜电位的去极化和细胞色素c的释放来表达这种抗凋亡功能。通过双杂交筛选，我们发现6-16蛋白与钙和整合素结合蛋白CIB/KIP/Calmyrin(CIB)相互作用，该蛋白与阿尔茨海默病相关蛋白早老素2相互作用。这些蛋白质的相互作用可能在细胞凋亡的调控中起着关键作用，这需要进一步的详细分析。这些结果表明，6-16蛋白可能通过抑制线粒体介导的细胞凋亡而发挥细胞存活蛋白的功能。
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.