Department of Biological Sciences, Sungkyunkwan University, Suwon, 440-746, Korea.
Mol Cells. 2010 Oct;30(4):355-62. doi: 10.1007/s10059-010-0134-8. Epub 2010 Sep 10.
c-Myc is a cellular onco-protein and a transcriptional activator important for cell growth, cell division, and tumorigenesis. Despite all that is known of its function, the mechanism of how c-Myc contributes to tumorigenesis is unclear. To gain insight into the mechanism through which c-Myc protein exerts its oncogenic activity, we performed large-scale, tandem repeat affinity purification and identified the F box only protein 8 (FBX8), an F-box- and Sec7 domain-containing protein, as a novel Myc-binding protein. The c-Myc/FBX8 interaction was mediated by the c-Myc box II (MBII) region. We also confirmed that Myc protein overexpression in 293T cells affected FBX8 cellular translocation and led to recovery from FBX8-mediated inhibition of ADP-ribosylation factor 6 (ARF6) function during cell invasion. Together, these results suggest that FBX8 is a novel c-Myc binding protein and that c-Myc induces cell invasive activity through the inhibition of FBX8 effects on ARF6 function during cell invasion.
c-Myc 是一种细胞癌蛋白，是一种转录激活因子，对细胞生长、细胞分裂和肿瘤发生很重要。尽管人们对其功能有了一定的了解，但 c-Myc 促进肿瘤发生的机制尚不清楚。为了深入了解 c-Myc 蛋白发挥致癌活性的机制，我们进行了大规模串联重复亲和纯化实验，鉴定出 F 框仅蛋白 8（FBX8）是一种新型的 Myc 结合蛋白，它是一种含有 F 框和 Sec7 结构域的蛋白质。c-Myc/FBX8 相互作用由 c-Myc 盒 II（MBII）区域介导。我们还证实，293T 细胞中 Myc 蛋白的过表达影响了 FBX8 的细胞易位，并导致在细胞侵袭过程中，FBX8 介导的 ARF6 功能抑制恢复。总之，这些结果表明 FBX8 是一种新型的 c-Myc 结合蛋白，c-Myc 通过抑制 FBX8 在细胞侵袭过程中对 ARF6 功能的影响，诱导细胞侵袭活性。
