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Inhibitory effect of shionone on activity of ubiquitin-specific protease 2

XIE Wen-juan1, QIN Dong-jun1, ZHANG Jian1, ZHOU Hu-chen2, WU Ying-li1   

  1. 1.Department of Pathophysiology, the Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of Education, Basic Medicine Faculty of Shanghai Jiao Tong University, Shanghai 200025, China; 2.School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
  • Online:2014-11-28 Published:2014-12-02
  • Supported by:

    NationalNaturalScienceFoundationofChina, 81272886

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Abstract:

Objective To identify new ubiquitin-specific protease 2 (USP2) inhibitors from natural compounds. Methods The Ub-CHOP-Reporter Kit was used to screen USP2 inhibitors. NB4 cells were treated by shionone (SH) of 100 μmol/L for different periods of time. Variations of the expression of USP2 targeted protein Cyclin D1 were detected by the Western blotting. The distribution of cell cycle was detected by the flow cytometry and molecular docking was used to analyze the binding of SH and USP2. Results The results of screening in vitro showed that SH inhibited the activity of USP2 with the 50% inhibition concentration (IC50) of 69 μmol/L. The results of Western blotting indicated that SH led to the decrease of Cyclin D1 expression. The results of flow cytometry showed that typical apoptotic peak (Sub-G1 peak) appeared and cells in S and G2/M phases decreased after being treated by SH for 48 h. The results of molecular docking indicated that the oxygen atom and skeleton core of SH and K503, W439, R363, and D440 of USP2 were essential for the binding of SH and USP2. Conclusion SH can inhibit the activity of USP2 and provide a lead compound for future development of new USP2 inhibitors.

Key words: ubiquitin-specific protease 2, inhibitor, shionone, molecular docking