Yang Liuzhong, Tang Zheng, Zhang Huiqiang, Kou Weizheng, Lu Zhihong, Li Xiaorui, Li Qiuping, Miao Zhanhui
Cancer Department of First Affiliated Hospital of Xinxiang Medical College Xinxiang, Henna, China.
Cell Physiol Biochem. 2013;31(6):952-9. doi: 10.1159/000350113. Epub 2013 Jun 26.
BACKGROUND/AIMS: Recent reports showed that proteasome subunit alpha type-7 (PSMA7) was overexpressed in colorectal cancer. To investigate the mechanism of PSMA7 in promotion of colorectal cancer, we screened for its interaction partners.
This study found that PSMA7 associated with nucleotide-binding oligomerization domain-containing protein 1 (NOD1) by yeast two-hybrid screening, co-immunoprecipitation (IP), and GST-pull down assay. As shown by Western blotting and ubiquitin assay, PSMA7 downregulated the expression of NOD1 in a proteasome-dependent manner. Overexpression of PSMA7 in HCT116 cells resulted in an inhibition of NOD1-mediated apoptosis and NF-κB activation, whereas knockdown of PSMA7 by RNA interference enhanced NOD1 activity.
Our data suggest that PSMA7 is a negative regulator of the NOD1, and may promote tumor growth by its inhibitory role on NOD1.
背景/目的：最近的报告显示，蛋白酶体亚基α7型（PSMA7）在结直肠癌中过表达。为了研究PSMA7促进结直肠癌的机制，我们筛选了其相互作用伙伴。
本研究通过酵母双杂交筛选、免疫共沉淀（IP）和GST下拉实验发现PSMA7与含核苷酸结合寡聚化结构域蛋白1（NOD1）相关。蛋白质印迹法和泛素检测显示，PSMA7以蛋白酶体依赖的方式下调NOD1的表达。在HCT116细胞中过表达PSMA7导致NOD1介导的细胞凋亡和NF-κB激活受到抑制，而通过RNA干扰敲低PSMA7则增强了NOD1的活性。
我们的数据表明，PSMA7是NOD1的负调节因子，可能通过对NOD1的抑制作用促进肿瘤生长。
