F-box protein FBXL2 inhibits gastric cancer proliferation by ubiquitin-mediated degradation of forkhead box M1

FEBS Letters
Liang-qing LiWen-jun Xie

Abstract

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.

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Citations

Sep 21, 2017·Oncology Letters·Qiang YuShichun Lu
Sep 14, 2018·Cell Communication and Signaling : CCS·Guo-Bin LiaoJian-Ying Bai
Mar 11, 2020·Cell Death & Disease·Zhe ChenYu Hou
Nov 26, 2020·Open Biology·Bethany Mason, Heike Laman
Jan 16, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Yi LiuZe Li
Sep 24, 2019·Cancer Letters·Min LinZhi-Wei Wang
Nov 5, 2019·Biochemical and Biophysical Research Communications·Yasuhiro UedaMichio Asahi

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