c-Myc Stimulates Cell Invasion by Inhibiting FBX8 Function
c-Myc Stimulates Cell Invasion by Inhibiting FBX8 Function
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DOI：
10.1007/s10059-010-0134-8
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发表时间：
2010-10-01
影响因子：
3.8
通讯作者：
Kim, Hongtae
中科院分区：
文献类型：
--
作者：
Cho, Hyun Jung;Oh, Yun Jeong;Kim, Hongtae
C-Myc是一种细胞癌蛋白和转录激活剂，对细胞生长、细胞分裂和肿瘤发生具有重要作用。尽管c-Myc的功能已为人所知，但c-Myc如何参与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、串联重复序列的亲和纯化，并鉴定出含有F-box和sec7结构域的F盒蛋白8(FBX8)是一种新的Myc结合蛋白。C-Myc/FBX8的相互作用是由c-Myc box II(MBII)区域介导的。我们还证实了在293T细胞中Myc蛋白的过表达影响了FBX8细胞的易位，并导致了FBX8在细胞侵袭过程中对ADP-核糖化因子6(ARF6)功能的抑制。综上所述，这些结果表明FBX8是一种新的c-Myc结合蛋白，c-Myc在细胞侵袭过程中通过抑制FBX8对ARF6功能的影响而诱导细胞侵袭活动。
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.