Yordy John S, Li Runzhao, Sementchenko Victor I, Pei Huiping, Muise-Helmericks Robin C, Watson Dennis K
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Oncogene. 2004 Aug 26;23(39):6654-65. doi: 10.1038/sj.onc.1207891.
The ETS1 transcription factor is a member of the Ets family of conserved sequence-specific DNA-binding proteins. ETS1 has been shown to play important roles in various cellular processes such as proliferation, differentiation, lymphoid development, motility, invasion and angiogenesis. These diverse roles of ETS1 are likely to be dependent on specific protein interactions. To identify proteins that interact with ETS1, a yeast two-hybrid screen was conducted. Here, we describe the functional interaction between SP100 and ETS1. SP100 protein interacts with ETS1 both in vitro and in vivo. SP100 is localized to nuclear bodies and ETS1 expression alters the nuclear body morphology in living cells. SP100 negatively modulates ETS1 transcriptional activation of the MMP1 and uPA promoters in a dose-dependent manner, decreases the expression of these endogenous genes, and reduces ETS1 DNA binding. Expression of SP100 inhibits the invasion of breast cancer cells and is induced by Interferon-alpha, which has been shown to inhibit the invasion of cancer cells. These data demonstrate that SP100 modulates ETS1-dependent biological processes.
ETS1转录因子是Ets家族中保守的序列特异性DNA结合蛋白的成员之一。已表明ETS1在各种细胞过程中发挥重要作用,如增殖、分化、淋巴细胞发育、迁移、侵袭和血管生成。ETS1的这些不同作用可能依赖于特定的蛋白质相互作用。为了鉴定与ETS1相互作用的蛋白质,进行了酵母双杂交筛选。在此,我们描述了SP100与ETS1之间的功能相互作用。SP100蛋白在体外和体内均与ETS1相互作用。SP100定位于核体,ETS1的表达改变活细胞中的核体形态。SP100以剂量依赖性方式负向调节MMP1和uPA启动子的ETS1转录激活,降低这些内源性基因的表达,并减少ETS1与DNA的结合。SP100的表达抑制乳腺癌细胞的侵袭,并由α干扰素诱导,α干扰素已被证明可抑制癌细胞的侵袭。这些数据表明SP100调节依赖于ETS1的生物学过程。