Lee Caroline G L, Ren Jianwei, Cheong Ian S Y, Ban Kenneth H K, Ooi London L P J, Yong Tan Soo, Kan Alison, Nuchprayoon Issarang, Jin Rongxian, Lee Kang-Hoe, Choti Michael, Lee Linda A
Department of Biochemistry, National University of Singapore, Singapore.
Oncogene. 2003 May 1;22(17):2592-603. doi: 10.1038/sj.onc.1206337.
The ubiquitin-like modifier (UBL) family has recently generated much interest in the scientific community, as it is implicated to play important regulatory roles via novel protein-protein modification. FAT10 (diubiquitin) belongs to this family of proteins, comprising two ubiquitin-like moieties fused in tandem, and has been implicated to be involved in the maintenance of spindle integrity during mitosis. As FAT10 may play a role in the regulation of genomic stability, we examined if there is an association between FAT10 expression and hepatocellular carcinoma (HCC) or other cancers. Northern blot analyses revealed upregulation of FAT10 expression in the tumors of 90% of HCC patients. In situ hybridization as well as immunohistochemistry utilizing anti-FAT10 antibodies localized highest FAT10 expression in the nucleus of HCC hepatocytes rather than the surrounding immune and non-HCC cells. FAT10 expression was also found to be highly upregulated in other cancers of the gastrointestinal tract and female reproductive system. In conclusion, we demonstrated upregulation of FAT10 expression in various gastrointestinal and gynecological cancers. Its overexpression is unrelated to the general increase in protein synthesis or a general immune/inflammatory response to cancer. Rather, FAT10 may modulate tumorigenesis through its reported interaction with the MAD2 spindle-assembly checkpoint protein.
泛素样修饰因子（UBL）家族最近在科学界引起了广泛关注，因为它被认为通过新型蛋白质-蛋白质修饰发挥重要的调节作用。FAT10（双泛素）属于该蛋白质家族，由两个串联融合的泛素样部分组成，并被认为参与有丝分裂期间纺锤体完整性的维持。由于FAT10可能在基因组稳定性调节中发挥作用，我们研究了FAT10表达与肝细胞癌（HCC）或其他癌症之间是否存在关联。Northern印迹分析显示，90%的HCC患者肿瘤中FAT10表达上调。原位杂交以及使用抗FAT10抗体的免疫组织化学显示，HCC肝细胞而非周围免疫细胞和非HCC细胞的细胞核中FAT10表达最高。还发现FAT10表达在胃肠道和女性生殖系统的其他癌症中也高度上调。总之，我们证明了FAT10表达在各种胃肠道和妇科癌症中上调。其过表达与蛋白质合成的普遍增加或对癌症的一般免疫/炎症反应无关。相反，FAT10可能通过其与MAD2纺锤体组装检查点蛋白的报道相互作用来调节肿瘤发生。
