Sho Takuya, Tsukiyama Tadasuke, Sato Tomonobu, Kondo Takeshi, Cheng Jun, Saku Takashi, Asaka Masahiro, Hatakeyama Shigetsugu
Department of Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
Biochim Biophys Acta. 2011 Jun;1813(6):1245-53. doi: 10.1016/j.bbamcr.2011.03.018. Epub 2011 Apr 2.
Ataxia-telangiectasia (AT) is an autosomal recessive genetic disease characterized by immunological deficiencies, neurological degeneration, developmental abnormalities and an increased risk of cancer. Ataxia-telangiectasia group D (ATDC) was initially described as a gene related to AT. Ataxia-telangiectasia group D, also known as TRIM29, is structurally a member of the tripartite motif (TRIM) family of proteins, some of which have been reported to be highly expressed in some human carcinomas, but the involvement of TRIM29 in carcinogenesis has not been fully elucidated. In this study, we found by using yeast two-hybrid screening that TRIM29 binds to Tip60, which has been reported as a cellular acetyltransferase protein. Overexpression of TRIM29 promoted degradation and changed localization of Tip60 and reduced acetylation of p53 at lysine 120 by Tip60, resulting in enhancement of cell growth and transforming activity. In addition, we found that TRIM29 suppresses apoptosis induced by UV irradiation in HCT116 cell lines. These findings suggest that TRIM29 functions as an oncogene that promotes tumor growth.
共济失调毛细血管扩张症（AT）是一种常染色体隐性遗传病，其特征为免疫缺陷、神经退行性变、发育异常以及患癌风险增加。共济失调毛细血管扩张症D组（ATDC）最初被描述为一种与AT相关的基因。共济失调毛细血管扩张症D组，也称为TRIM29，在结构上是三重模体（TRIM）蛋白家族的成员，据报道其中一些在某些人类癌症中高度表达，但TRIM29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TRIM29与Tip60结合，Tip60据报道是一种细胞乙酰转移酶蛋白。TRIM29的过表达促进了Tip60的降解并改变了其定位，降低了Tip60对p53赖氨酸120位点的乙酰化作用，导致细胞生长和转化活性增强。此外，我们发现TRIM29抑制HCT116细胞系中紫外线照射诱导的细胞凋亡。这些发现表明TRIM29作为一种癌基因发挥作用，促进肿瘤生长。
