Sugiura Takeyuki, Miyamoto Kentaro
Discovery Research Laboratory, Tokyo R&D Center, Daiichi Pharmaceutical Co., Ltd., Daiichi-Sankyo Group, 16-13, Kitakasai 1-Chome, Edogawa-ku, Tokyo 134-8630, Japan.
J Cell Biochem. 2008 Nov 1;105(4):1081-91. doi: 10.1002/jcb.21908.
To explore the molecules associated with gastric adenocarcinoma, we used the gene expression profile database of various human tissues and identified TRIM31 upregulated in both patients with chronic gastritis and stomach cancer. TRIM31 is a new member of RBCC proteins composed of RING finger, B-box and coiled-coil domains. We characterized TRIM31 biochemically and found it possess properties in common with other RBCC proteins, such as occurrence of alternative splicing transcripts, in vitro autoubiquitylating activity and a tendency to homo-oligomerize. The primary localization site of TRIM31 is the cytoplasm but some fraction is potentially associated with the mitochondria. TRIM31 overexpression suppresses colony formation of HCT116 cells while knockdown of its expression with short interfering RNAs (siRNAs) consistently tends to enhance growth of AsPC-1 cells slightly. Thus, TRIM31 is a characteristic RBCC protein with the ability to regulate cell proliferation negatively and may be a potential biomarker of gastric cancer as it is overexpressed from the early stage of gastric carcinogenesis.
为了探索与胃腺癌相关的分子,我们利用了各种人类组织的基因表达谱数据库,并鉴定出在慢性胃炎患者和胃癌患者中均上调的TRIM31。TRIM31是由RING指结构域、B盒结构域和卷曲螺旋结构域组成的RBCC蛋白家族的新成员。我们对TRIM31进行了生化特性分析,发现它具有与其他RBCC蛋白相同的特性,如存在可变剪接转录本、体外自泛素化活性以及同源寡聚化倾向。TRIM31的主要定位位点是细胞质,但有一部分可能与线粒体相关。TRIM31的过表达抑制HCT116细胞的集落形成,而用小干扰RNA(siRNA)敲低其表达则始终倾向于略微增强AsPC-1细胞的生长。因此,TRIM31是一种具有负向调节细胞增殖能力的特征性RBCC蛋白,并且由于其在胃癌发生的早期阶段就过度表达,可能是胃癌的潜在生物标志物。