Li Liang-qing, Pan Dun, Chen Hui, Zhang Lin, Xie Wen-jun
Department of Gastrointestinal Surgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, China.
FEBS Lett. 2016 Feb;590(4):445-52. doi: 10.1002/1873-3468.12071. Epub 2016 Feb 8.
F-box/LRR-repeat protein 2 (FBXL2), a component of Skp-Cullin-F box (SCF) ubiquitin E3 ligase, has been shown to inhibit tumorigenesis by targeting and ubiquitinating several oncoproteins. However, its role in gastric cancer remains poorly understood. Here, by tandem mass spectrometry, we show that FBXL2 interacts with forkhead box M1 (FoxM1) transcription factor. As a result, FBXL2 promotes ubiquitination and degradation of FoxM1 in gastric cancer cells. Furthermore, overexpression of FBXL2 inhibits, while its deficiency promotes cell proliferation and invasion. Expression levels of cell-cycle regulators (Cdc25B and p27), which are down-stream target effectors of FoxM1, are also regulated by FBXL2. Therefore, our results uncover a previous unknown network involving FBXL2 and FoxM1 in the regulation of gastric cancer growth.
F-box/富含亮氨酸重复序列蛋白2（FBXL2）是Skp-Cullin-F盒（SCF）泛素E3连接酶的一个组成部分，已被证明可通过靶向并泛素化几种癌蛋白来抑制肿瘤发生。然而，其在胃癌中的作用仍知之甚少。在此，通过串联质谱分析，我们发现FBXL2与叉头框M1（FoxM1）转录因子相互作用。结果，FBXL2促进胃癌细胞中FoxM1的泛素化和降解。此外，FBXL2的过表达抑制，而其缺失则促进细胞增殖和侵袭。细胞周期调节因子（Cdc25B和p27）的表达水平，作为FoxM1的下游靶效应器，也受到FBXL2的调节。因此，我们的结果揭示了一个先前未知的涉及FBXL2和FoxM1的网络在胃癌生长调控中的作用。
