Kano Satoshi, Miyajima Naoto, Fukuda Satoshi, Hatakeyama Shigetsugu
Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
Cancer Res. 2008 Jul 15;68(14):5572-80. doi: 10.1158/0008-5472.CAN-07-6231.
Tripartite motif protein 32 (TRIM32) mRNA has been reported to be highly expressed in human head and neck squamous cell carcinoma, but the involvement of TRIM32 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that TRIM32 binds to Abl-interactor 2 (Abi2), which is known as a tumor suppressor and a cell migration inhibitor, and we showed that TRIM32 mediates the ubiquitination of Abi2. Overexpression of TRIM32 promoted degradation of Abi2, resulting in enhancement of cell growth, transforming activity, and cell motility, whereas a dominant-negative mutant of TRIM32 lacking the RING domain inhibited the degradation of Abi2. In addition, we found that TRIM32 suppresses apoptosis induced by cis-diamminedichloroplatinum (II) in HEp2 cell lines. These findings suggest that TRIM32 is a novel oncogene that promotes tumor growth, metastasis, and resistance to anticancer drugs.
据报道，三联基序蛋白32（TRIM32）信使核糖核酸（mRNA）在人类头颈部鳞状细胞癌中高表达，但TRIM32在致癌过程中的作用尚未完全阐明。在本研究中，我们通过酵母双杂交筛选发现TRIM32与Abl相互作用蛋白2（Abi2）结合，Abi2是一种已知的肿瘤抑制因子和细胞迁移抑制剂，并且我们表明TRIM32介导Abi2的泛素化。TRIM32过表达促进Abi2降解，导致细胞生长、转化活性和细胞运动性增强，而缺乏RING结构域的TRIM32显性负突变体抑制Abi2降解。此外，我们发现TRIM32抑制顺二氯二氨铂（II）诱导的HEp2细胞系凋亡。这些发现表明TRIM32是一种促进肿瘤生长、转移及抗癌药物耐药性的新型癌基因。
